An aberrant form of human CHROMOSOME 22 characterized by translocation of the distal end of chromosome 9 from 9q34, to the long arm of chromosome 22 at 22q11. It is present in the bone marrow cells of 80 to 90 per cent of patients with chronic myelocytic leukemia (LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE).
The short, acrocentric human chromosomes, called group G in the human chromosome classification. This group consists of chromosome pairs 21 and 22 and the Y chromosome.
Clonal hematopoetic disorder caused by an acquired genetic defect in PLURIPOTENT STEM CELLS. It starts in MYELOID CELLS of the bone marrow, invades the blood and then other organs. The condition progresses from a stable, more indolent, chronic phase (LEUKEMIA, MYELOID, CHRONIC PHASE) lasting up to 7 years, to an advanced phase composed of an accelerated phase (LEUKEMIA, MYELOID, ACCELERATED PHASE) and BLAST CRISIS.
Translation products of a fusion gene derived from CHROMOSOMAL TRANSLOCATION of C-ABL GENES to the genetic locus of the breakpoint cluster region gene on chromosome 22. Several different variants of the bcr-abl fusion proteins occur depending upon the precise location of the chromosomal breakpoint. These variants can be associated with distinct subtypes of leukemias such as PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA; LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE; and NEUTROPHILIC LEUKEMIA, CHRONIC.
In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Any method used for determining the location of and relative distances between genes on a chromosome.
BENZOIC ACID amides.
An advanced phase of chronic myelogenous leukemia, characterized by a rapid increase in the proportion of immature white blood cells (blasts) in the blood and bone marrow to greater than 30%.
Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS.
A specific pair of GROUP G CHROMOSOMES of the human chromosome classification.
A myelodysplastic/myeloproliferative disorder characterized by myelodysplasia associated with bone marrow and peripheral blood patterns similar to CHRONIC MYELOID LEUKEMIA, but cytogenetically lacking a PHILADELPHIA CHROMOSOME or bcr/abl fusion gene (GENES, ABL).
Mapping of the KARYOTYPE of a cell.
Proto-oncogene protein bcr is a serine-threonine kinase that functions as a negative regulator of CELL PROLIFERATION and NEOPLASTIC CELL TRANSFORMATION. It is commonly fused with cellular abl protein to form BCR-ABL FUSION PROTEINS in PHILADELPHIA CHROMOSOME positive LEUKEMIA patients.
A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
A neoplasm characterized by abnormalities of the lymphoid cell precursors leading to excessive lymphoblasts in the marrow and other organs. It is the most common cancer in children and accounts for the vast majority of all childhood leukemias.
A specific pair of GROUP C CHROMSOMES of the human chromosome classification.
The phase of chronic myeloid leukemia following the chronic phase (LEUKEMIA, MYELOID, CHRONIC-PHASE), where there are increased systemic symptoms, worsening cytopenias, and refractory LEUKOCYTOSIS.
The initial phase of chronic myeloid leukemia consisting of an relatively indolent period lasting from 4 to 7 years. Patients range from asymptomatic to those exhibiting ANEMIA; SPLENOMEGALY; and increased cell turnover. There are 5% or fewer blast cells in the blood and bone marrow in this phase.
A subdiscipline of genetics which deals with the cytological and molecular analysis of the CHROMOSOMES, and location of the GENES on chromosomes, and the movements of chromosomes during the CELL CYCLE.
A type of chromosome aberration characterized by CHROMOSOME BREAKAGE and transfer of the broken-off portion to another location, often to a different chromosome.
Form of leukemia characterized by an uncontrolled proliferation of the myeloid lineage and their precursors (MYELOID PROGENITOR CELLS) in the bone marrow and other sites.
The medium-sized, submetacentric human chromosomes, called group C in the human chromosome classification. This group consists of chromosome pairs 6, 7, 8, 9, 10, 11, and 12 and the X chromosome.
Retrovirus-associated DNA sequences (abl) originally isolated from the Abelson murine leukemia virus (Ab-MuLV). The proto-oncogene abl (c-abl) codes for a protein that is a member of the tyrosine kinase family. The human c-abl gene is located at 9q34.1 on the long arm of chromosome 9. It is activated by translocation to bcr on chromosome 22 in chronic myelogenous leukemia.
Clinical conditions caused by an abnormal chromosome constitution in which there is extra or missing chromosome material (either a whole chromosome or a chromosome segment). (from Thompson et al., Genetics in Medicine, 5th ed, p429)
Staining of bands, or chromosome segments, allowing the precise identification of individual chromosomes or parts of chromosomes. Applications include the determination of chromosome rearrangements in malformation syndromes and cancer, the chemistry of chromosome segments, chromosome changes during evolution, and, in conjunction with cell hybridization studies, chromosome mapping.
The female sex chromosome, being the differential sex chromosome carried by half the male gametes and all female gametes in human and other male-heterogametic species.
The homologous chromosomes that are dissimilar in the heterogametic sex. There are the X CHROMOSOME, the Y CHROMOSOME, and the W, Z chromosomes (in animals in which the female is the heterogametic sex (the silkworm moth Bombyx mori, for example)). In such cases the W chromosome is the female-determining and the male is ZZ. (From King & Stansfield, A Dictionary of Genetics, 4th ed)
A rare myeloproliferative disorder that is characterized by a sustained, mature neutrophilic leukocytosis. No monocytosis, EOSINOPHILIA, or basophilia is present, nor is there a PHILADELPHIA CHROMOSOME or bcr-abl fusion gene (GENES, ABL).
A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification.
Very long DNA molecules and associated proteins, HISTONES, and non-histone chromosomal proteins (CHROMOSOMAL PROTEINS, NON-HISTONE). Normally 46 chromosomes, including two sex chromosomes are found in the nucleus of human cells. They carry the hereditary information of the individual.
The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.
A type of IN SITU HYBRIDIZATION in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei.
Structures within the nucleus of bacterial cells consisting of or containing DNA, which carry genetic information essential to the cell.
The orderly segregation of CHROMOSOMES during MEIOSIS or MITOSIS.
Leisure activities engaged in for pleasure.
A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.
A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.
Actual loss of portion of a chromosome.
The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development.
Therapeutic act or process that initiates a response to a complete or partial remission level.
A specific pair of GROUP E CHROMOSOMES of the human chromosome classification.
Examination of CHROMOSOMES to diagnose, classify, screen for, or manage genetic diseases and abnormalities. Following preparation of the sample, KARYOTYPING is performed and/or the specific chromosomes are analyzed.
A specific pair GROUP C CHROMSOMES of the human chromosome classification.
A specific pair of GROUP G CHROMOSOMES of the human chromosome classification.
Complex nucleoprotein structures which contain the genomic DNA and are part of the CELL NUCLEUS of PLANTS.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
Structures within the nucleus of fungal cells consisting of or containing DNA, which carry genetic information essential to the cell.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
Non-receptor tyrosine kinases encoded by the C-ABL GENES. They are distributed in both the cytoplasm and the nucleus. c-Abl plays a role in normal HEMATOPOIESIS especially of the myeloid lineage. Oncogenic transformation of c-abl arises when specific N-terminal amino acids are deleted, releasing the kinase from negative regulation.
The phase of cell nucleus division following PROMETAPHASE, in which the CHROMOSOMES line up across the equatorial plane of the SPINDLE APPARATUS prior to separation.
Genes whose gain-of-function alterations lead to NEOPLASTIC CELL TRANSFORMATION. They include, for example, genes for activators or stimulators of CELL PROLIFERATION such as growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. A prefix of "v-" before oncogene symbols indicates oncogenes captured and transmitted by RETROVIRUSES; the prefix "c-" before the gene symbol of an oncogene indicates it is the cellular homolog (PROTO-ONCOGENES) of a v-oncogene.
Leukemia associated with HYPERPLASIA of the lymphoid tissues and increased numbers of circulating malignant LYMPHOCYTES and lymphoblasts.
A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification.
A specific pair of GROUP E CHROMOSOMES of the human chromosome classification.
The alignment of CHROMOSOMES at homologous sequences.
Complex nucleoprotein structures which contain the genomic DNA and are part of the CELL NUCLEUS of MAMMALS.
A specific pair of GROUP D CHROMOSOMES of the human chromosome classification.
A specific pair of GROUP B CHROMOSOMES of the human chromosome classification.
A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Remnant of a tumor or cancer after primary, potentially curative therapy. (Dr. Daniel Masys, written communication)
The human male sex chromosome, being the differential sex chromosome carried by half the male gametes and none of the female gametes in humans.
A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.
A specific pair of GROUP F CHROMOSOMES of the human chromosome classification.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
DNA constructs that are composed of, at least, a REPLICATION ORIGIN, for successful replication, propagation to and maintenance as an extra chromosome in bacteria. In addition, they can carry large amounts (about 200 kilobases) of other sequence for a variety of bioengineering purposes.
The human female sex chromosome, being the differential sex chromosome carried by half the male gametes and all female gametes in humans.
The large, metacentric human chromosomes, called group A in the human chromosome classification. This group consists of chromosome pairs 1, 2, and 3.
A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.
A technique for visualizing CHROMOSOME ABERRATIONS using fluorescently labeled DNA probes which are hybridized to chromosomal DNA. Multiple fluorochromes may be attached to the probes. Upon hybridization, this produces a multicolored, or painted, effect with a unique color at each site of hybridization. This technique may also be used to identify cross-species homology by labeling probes from one species for hybridization with chromosomes from another species.
One of the two pairs of human chromosomes in the group B class (CHROMOSOMES, HUMAN, 4-5).
A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
A specific pair of GROUP D CHROMOSOMES of the human chromosome classification.
A leukemia/lymphoma found predominately in children and adolescents and characterized by a high number of lymphoblasts and solid tumor lesions. Frequent sites involve LYMPH NODES, skin, and bones. It most commonly presents as leukemia.
One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells. In addition to antiviral activity, it activates NATURAL KILLER CELLS and B-LYMPHOCYTES, and down-regulates VASCULAR ENDOTHELIAL GROWTH FACTOR expression through PI-3 KINASE and MAPK KINASES signaling pathways.
A specific pair of GROUP D CHROMOSOMES of the human chromosome classification.
A specific pair of GROUP E CHROMOSOMES of the human chromosome classification.
Time period from 2001 through 2100 of the common era.
The short, submetacentric human chromosomes, called group E in the human chromosome classification. This group consists of chromosome pairs 16, 17, and 18.
A specific pair of GROUP F CHROMOSOMES of the human chromosome classification.
Chromosomes in which fragments of exogenous DNA ranging in length up to several hundred kilobase pairs have been cloned into yeast through ligation to vector sequences. These artificial chromosomes are used extensively in molecular biology for the construction of comprehensive genomic libraries of higher organisms.
A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.
The medium-sized, acrocentric human chromosomes, called group D in the human chromosome classification. This group consists of chromosome pairs 13, 14, and 15.
Agents that inhibit PROTEIN KINASES.
The co-inheritance of two or more non-allelic GENES due to their being located more or less closely on the same CHROMOSOME.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
A type of chromosomal aberration involving DNA BREAKS. Chromosome breakage can result in CHROMOSOMAL TRANSLOCATION; CHROMOSOME INVERSION; or SEQUENCE DELETION.
The transference of BONE MARROW from one human or animal to another for a variety of purposes including HEMATOPOIETIC STEM CELL TRANSPLANTATION or MESENCHYMAL STEM CELL TRANSPLANTATION.
Aberrant chromosomes with no ends, i.e., circular.
Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Proto-oncogenes have names of the form c-onc.
An aberration in which a chromosomal segment is deleted and reinserted in the same place but turned 180 degrees from its original orientation, so that the gene sequence for the segment is reversed with respect to that of the rest of the chromosome.
A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event.
The mechanisms of eukaryotic CELLS that place or keep the CHROMOSOMES in a particular SUBNUCLEAR SPACE.
Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.
The large, submetacentric human chromosomes, called group B in the human chromosome classification. This group consists of chromosome pairs 4 and 5.
DNA present in neoplastic tissue.
Progenitor cells from which all blood cells derive.
Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.
A dosage compensation process occurring at an early embryonic stage in mammalian development whereby, at random, one X CHROMOSOME of the pair is repressed in the somatic cells of females.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)
Established cell cultures that have the potential to propagate indefinitely.
Highly proliferative, self-renewing, and colony-forming stem cells which give rise to NEOPLASMS.
The clear constricted portion of the chromosome at which the chromatids are joined and by which the chromosome is attached to the spindle during cell division.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
An antitumor alkaloid isolated from VINCA ROSEA. (Merck, 11th ed.)
Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Structures within the CELL NUCLEUS of insect cells containing DNA.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
A type of CELL NUCLEUS division, occurring during maturation of the GERM CELLS. Two successive cell nucleus divisions following a single chromosome duplication (S PHASE) result in daughter cells with half the number of CHROMOSOMES as the parent cells.
Any cell, other than a ZYGOTE, that contains elements (such as NUCLEI and CYTOPLASM) from two or more different cells, usually produced by artificial CELL FUSION.
Period after successful treatment in which there is no appearance of the symptoms or effects of the disease.
Structures which are contained in or part of CHROMOSOMES.
The short, metacentric human chromosomes, called group F in the human chromosome classification. This group consists of chromosome pairs 19 and 20.
The use of two or more chemicals simultaneously or sequentially in the drug therapy of neoplasms. The drugs need not be in the same dosage form.
A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function.
Transplantation between individuals of the same species. Usually refers to genetically disparate individuals in contradistinction to isogeneic transplantation for genetically identical individuals.
The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of CHROMOSOMES, chromosome pairs, or chromosome fragments. In a normally diploid cell (DIPLOIDY) the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is MONOSOMY (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is TRISOMY (symbol: 2N+1).
Elements of limited time intervals, contributing to particular results or situations.
A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.
Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.
Transfer of HEMATOPOIETIC STEM CELLS from BONE MARROW or BLOOD between individuals within the same species (TRANSPLANTATION, HOMOLOGOUS) or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS). Hematopoietic stem cell transplantation has been used as an alternative to BONE MARROW TRANSPLANTATION in the treatment of a variety of neoplasms.
The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.
Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.
The total relative probability, expressed on a logarithmic scale, that a linkage relationship exists among selected loci. Lod is an acronym for "logarithmic odds."
Deliberate breeding of two different individuals that results in offspring that carry part of the genetic material of each parent. The parent organisms must be genetically compatible and may be from different varieties or closely related species.
A variety of simple repeat sequences that are distributed throughout the GENOME. They are characterized by a short repeat unit of 2-8 basepairs that is repeated up to 100 times. They are also known as short tandem repeats (STRs).
Widely used technique which exploits the ability of complementary sequences in single-stranded DNAs or RNAs to pair with each other to form a double helix. Hybridization can take place between two complimentary DNA sequences, between a single-stranded DNA and a complementary RNA, or between two RNA sequences. The technique is used to detect and isolate specific sequences, measure homology, or define other characteristics of one or both strands. (Kendrew, Encyclopedia of Molecular Biology, 1994, p503)
Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease.
The prevailing temper or spirit of an individual or group in relation to the tasks or functions which are expected.
The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods.
Species- or subspecies-specific DNA (including COMPLEMENTARY DNA; conserved genes, whole chromosomes, or whole genomes) used in hybridization studies in order to identify microorganisms, to measure DNA-DNA homologies, to group subspecies, etc. The DNA probe hybridizes with a specific mRNA, if present. Conventional techniques used for testing for the hybridization product include dot blot assays, Southern blot assays, and DNA:RNA hybrid-specific antibody tests. Conventional labels for the DNA probe include the radioisotope labels 32P and 125I and the chemical label biotin. The use of DNA probes provides a specific, sensitive, rapid, and inexpensive replacement for cell culture techniques for diagnosing infections.
Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
Metacentric chromosomes produced during MEIOSIS or MITOSIS when the CENTROMERE splits transversely instead of longitudinally. The chromosomes produced by this abnormal division are one chromosome having the two long arms of the original chromosome, but no short arms, and the other chromosome consisting of the two short arms and no long arms. Each of these isochromosomes constitutes a simultaneous duplication and deletion.
The possession of a third chromosome of any one type in an otherwise diploid cell.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
The failure of homologous CHROMOSOMES or CHROMATIDS to segregate during MITOSIS or MEIOSIS with the result that one daughter cell has both of a pair of parental chromosomes or chromatids and the other has none.
The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.
A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.
DNA constructs that are composed of, at least, all elements, such as a REPLICATION ORIGIN; TELOMERE; and CENTROMERE, required for successful replication, propagation to and maintainance in progeny human cells. In addition, they are constructed to carry other sequences for analysis or gene transfer.
Large multiprotein complexes that bind the centromeres of the chromosomes to the microtubules of the mitotic spindle during metaphase in the cell cycle.
A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs.
An individual having different alleles at one or more loci regarding a specific character.
A technique with which an unknown region of a chromosome can be explored. It is generally used to isolate a locus of interest for which no probe is available but that is known to be linked to a gene which has been identified and cloned. A fragment containing a known gene is selected and used as a probe to identify other overlapping fragments which contain the same gene. The nucleotide sequences of these fragments can then be characterized. This process continues for the length of the chromosome.
Nucleoproteins, which in contrast to HISTONES, are acid insoluble. They are involved in chromosomal functions; e.g. they bind selectively to DNA, stimulate transcription resulting in tissue-specific RNA synthesis and undergo specific changes in response to various hormones or phytomitogens.
An increased tendency to acquire CHROMOSOME ABERRATIONS when various processes involved in chromosome replication, repair, or segregation are dysfunctional.
A microtubule structure that forms during CELL DIVISION. It consists of two SPINDLE POLES, and sets of MICROTUBULES that may include the astral microtubules, the polar microtubules, and the kinetochore microtubules.
Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.
A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.
Susceptibility of chromosomes to breakage leading to translocation; CHROMOSOME INVERSION; SEQUENCE DELETION; or other CHROMOSOME BREAKAGE related aberrations.
Variation occurring within a species in the presence or length of DNA fragment generated by a specific endonuclease at a specific site in the genome. Such variations are generated by mutations that create or abolish recognition sites for these enzymes or change the length of the fragment.
Genetic loci associated with a QUANTITATIVE TRAIT.
The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the MAJOR HISTOCOMPATIBILITY COMPLEX.
An aberration in which an extra chromosome or a chromosomal segment is made.
Highly repetitive DNA sequences found in HETEROCHROMATIN, mainly near centromeres. They are composed of simple sequences (very short) (see MINISATELLITE REPEATS) repeated in tandem many times to form large blocks of sequence. Additionally, following the accumulation of mutations, these blocks of repeats have been repeated in tandem themselves. The degree of repetition is on the order of 1000 to 10 million at each locus. Loci are few, usually one or two per chromosome. They were called satellites since in density gradients, they often sediment as distinct, satellite bands separate from the bulk of genomic DNA owing to a distinct BASE COMPOSITION.
A species of fruit fly much used in genetics because of the large size of its chromosomes.
Conditions which cause proliferation of hemopoietically active tissue or of tissue which has embryonic hemopoietic potential. They all involve dysregulation of multipotent MYELOID PROGENITOR CELLS, most often caused by a mutation in the JAK2 PROTEIN TYROSINE KINASE.
Sequences of DNA or RNA that occur in multiple copies. There are several types: INTERSPERSED REPETITIVE SEQUENCES are copies of transposable elements (DNA TRANSPOSABLE ELEMENTS or RETROELEMENTS) dispersed throughout the genome. TERMINAL REPEAT SEQUENCES flank both ends of another sequence, for example, the long terminal repeats (LTRs) on RETROVIRUSES. Variations may be direct repeats, those occurring in the same direction, or inverted repeats, those opposite to each other in direction. TANDEM REPEAT SEQUENCES are copies which lie adjacent to each other, direct or inverted (INVERTED REPEAT SEQUENCES).
The chromosomal constitution of cells, in which each type of CHROMOSOME is represented twice. Symbol: 2N or 2X.
The process of cumulative change at the level of DNA; RNA; and PROTEINS, over successive generations.
Either of the two longitudinally adjacent threads formed when a eukaryotic chromosome replicates prior to mitosis. The chromatids are held together at the centromere. Sister chromatids are derived from the same chromosome. (Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication.
Standards or regulations for construction which are designed to ensure safety against electrical hazards, fires, etc.
The occurrence in an individual of two or more cell populations of different chromosomal constitutions, derived from a single ZYGOTE, as opposed to CHIMERISM in which the different cell populations are derived from more than one zygote.
Tetracyclic spiro-BENZAZEPINES isolated from the seeds of CEPHALOTAXUS. They are esters of the alkaloid cephalotaxine and may be effective as antineoplastic agents.
The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.

Autografting with philadelphia chromosome-negative mobilized hematopoietic progenitor cells in chronic myelogenous leukemia. (1/390)

Intensive chemotherapy given in early chronic phase of chronic myelogenous leukemia (CML) has resulted in high numbers of circulating Philadelphia (Ph) chromosome-negative hematopoietic progenitor cells (HPC). We have autografted 30 consecutive patients with CML in chronic phase with HPC collected in this way to facilitate restoration of Ph-negative hematopoiesis in bone marrow after high-dose therapy. Hematopoietic recovery to greater than 0.5 x10(9)/L neutrophils and to greater than 25 x 10(9)/L platelets occurred in all patients, a median of 13 (range, 9 to 32) days and 16 (range, 6 to 106) days postautograft, respectively. Regenerating marrow cells were Ph-negative in 16 (53%) patients and greater than 66% Ph-negative in 10 (33%) patients. Twenty-eight patients are alive 6 to 76 months (median, 24 months) after autografting. Three patients have developed blast crisis from which 2 have died. Eight patients are in complete cytogenetic remission at a median of 20 (range, 6 to 44) months with a median ratio BCR-ABL/ABL of 0.002 (range, <0.001 to 0.01). Eight patients are in major cytogenetic remission at a median of 22 (range, 6 to 48) months. No patient died as a consequence of the treatment. All patients had some degree of stomatitis that was severe in 15 (50%) patients. Gastrointestinal and hepatic toxicities were observed in about one fourth of patients. Thus, autografting with Ph-negative mobilized HPC can result in prolonged restoration of Ph-negative hematopoiesis for some patients with CML; moreover, most autograft recipients report normal or near normal activity levels, suggesting that this procedure need not to be associated either with prolonged convalescence or with chronic debility.  (+info)

Extremely high and specific activity of DNA enzymes in cells with a Philadelphia chromosome. (2/390)

BACKGROUND: Chronic myelogenous leukemia (CML) results from chromosome 22 translocations (the Philadelphia chromosome) that creates BCR-ABL fusion genes, which encode two abnormal mRNAs (b3a2 and b2a2). Various attempts to design antisense oligonucleotides that specifically cleave abnormal L6 BCR-ABL fusion mRNA have not been successful. Because b2a2 mRNA cannot be effectively cleaved by hammerhead ribozymes near the BCR-ABL junction, it has proved very difficult to engineer specific cleavage of this chimeric mRNA. Nonspecific effects associated with using antisense molecules make the use of such antisense molecules questionable. RESULTS: The usefulness of DNA enzymes in specifically suppressing expression of L6 BCR-ABL mRNA in mammalian cells is demonstrated. Although the efficacy of DNA enzymes with natural linkages decreased 12 hours after transfection, partially modified DNA enzymes, with either phosphorothioate or 2'-O-methyl groups at both their 5' and 3' ends, remained active for much longer times in mammalian cells. Moreover, the DNA enzyme with only 2'-O-methyl modifications was also highly specific for abnormal mRNA. CONCLUSIONS: DNA enzymes with 2'-O-methyl modifications are potentially useful as gene-inactivating agents in the treatment of diseases such as CML. In contrast to conventional antisense DNAs, some of the DNA enzymes used in this study were highly specific and cleaved only abnormal BCR-ABL mRNA.  (+info)

Selective induction of apoptosis in Philadelphia chromosome-positive chronic myelogenous leukemia cells by an inhibitor of BCR - ABL tyrosine kinase, CGP 57148. (3/390)

The BCR - ABL tyrosine kinase has been implicated as the cause of Philadelphia chromosome (Ph1)-positive leukemias. We report herein that CGP 57148, a selective inhibitor of the ABL tyrosine kinase, caused apoptosis specifically in bcr - abl-positive chronic myelogenous leukemia (CML) cells, K562 and KYO-1. Upon treatment with CGP 57148, CRKL, a specific substrate for BCR - ABL that propagates signals via phosphatidylinositol-3' kinase (PI3K), was dephosphorylated, indicating inhibition of BCR - ABL tyrosine kinase at the cellular level. Likewise, MAPK/ERK, a downstream mediator of Ras, was also dephosphorylated. Caspase activation and cleavage of retinoblastoma protein (pRB) accompanied the development of CGP 57148-induced apoptosis. Inhibition of caspase suppressed apoptosis and the cleavage of pRB, and in turn arrested cells in the G1 phase. These results indicate that CGP 57148 shows apoptogenic and anti-proliferative effects on bcr - abl-positive cells by blocking BCR - ABL-initiated signaling pathways.  (+info)

Relapse in chronic myeloid leukemia after bone marrow transplantation: biomathematical modeling as a new approach to understanding pathogenesis. (4/390)

A biomathematical model was developed to simulate relapse development in patients with chronic myeloid leukemia (CML) following bone marrow transplantation (BMT). The purpose of this study was to better understand the pathophysiology of the time evolution of CML relapse and to provide means whereby the outcomes of patients with CML relapse can be projected and treatment modified accordingly. The model consists of three parallel series of catenated compartments representing granulopoiesis in normal (donor) cells from the marrow, in CML cells from the marrow, and in CML cells from extramedullary sites. It was assumed that CML stem cells were resistant to feedback control and that CML-derived neutrophils, as well as normal neutrophils, exercised feedback regulation of normal stem cells. The known longer generation times for CML neutrophil precursors compared with normal neutrophil precursors were used, and it was assumed that 10(7) pluripotential stem cells were infused with BMT. The model was evaluated for its ability to simulate the reappearance of CML (Philadelphia chromosome positive) metaphases in the marrow and the recovery pattern in the blood neutrophil count in six patients who had relapsed following BMT (allogeneic in three patients, allogeneic with T-cell depletion in two patients, and syngeneic in one patient). The variables tested included the site of origin of the CML stem cells responsible for relapse (marrow alone versus marrow and extramedullary sites), the minimum number of CML stem cells responsible for relapse, and the time delay between BMT and the onset of relapse. Model profiles based on the observed values were obtained in each case. The simulations pointed to the fact that relapse began from a small number of CML cells in medullary and extramedullary sites. The time delay between BMT and the onset of relapse varied from 15 to 240 days. We suggest that this biomathematical model should be further investigated as a possible means of predicting outcome and guiding the treatment for patients with CML relapsing after BMT.  (+info)

The prognostic significance of p16INK4a/p14ARF and p15INK4b deletions in adult acute lymphoblastic leukemia. (5/390)

Cytogenetic/molecular abnormalities significantly influence the prognosis of patients with acute leukemia. Recently, two genes, p16INK4a and p15INK4b, encoding two cyclin-dependent kinase inhibitor proteins of the INK4 family of Mr 15,000 and 16,000, respectively, have been localized to 9p21. Remarkably, the p16INK4a locus has been found to encode a second protein, p14ARF, known as p19ARF in mice, with a distinct reading frame. Like p16INK4a, p14ARF is involved in cell cycle regulation, blocking cells at the G1 restriction point through the activity of MDM-2 and p53. We studied bone marrow samples of 42 newly diagnosed and untreated patients with acute lymphoblastic leukemia for the incidence of deletions of p16INK4a/p14ARF and p15INK4b using Southern blot analysis and determined the clinical outcome with regard to complete remission (CR) duration, event-free survival, and overall survival. We found deletions of p16INK4a/p14ARF in 17 of 42 patients (40%), with homozygous deletions in 11 of 42 patients (26%) and hemizygous deletions in 6 of 42 patients (14%). The gene for p15INK4b was codeleted in most, but not all, cases and was never deleted without deletion of p16INK4a/ p14ARF. No correlation was observed between molecular studies and karyotype abnormalities as determined by conventional cytogenetics. Furthermore, no difference was found in the CR rate, CR duration, event-free survival, and overall survival in patients with homozygous gene deletions compared to patients with no deletions or loss of only one allele.  (+info)

BCR/ABL mRNA and the P210(BCR/ABL) protein are downmodulated by interferon-alpha in chronic myeloid leukemia patients. (6/390)

The BCR/ABL hybrid gene plays a central role in the pathogenesis of the chronic phase of chronic myeloid leukemia (CML). We used a very sensitive quantitative reverse transcriptase-polymerase chain reaction to investigate the levels of hybrid BCR/ABL mRNA in bone marrow cells of 20 patients with Philadelphia positive (Ph(+)) CML treated with interferon-alpha (IFN-alpha) as a single agent. Bone marrow samples were collected at diagnosis and at hematologic remission induced by IFN-alpha, or by hydroxyurea in case of resistance to IFN-alpha. The mean levels of BCR/ABL transcripts in bone marrow mononuclear cells of patients who showed a complete hematologic response to IFN-alpha were significantly reduced with respect to those at diagnosis (48 x 10(3) v 168 x 10(3); P <.001), whereas no difference was detected between the values at diagnosis and at hematologic remission in patients resistant to IFN-alpha. In cell culture experiments, IFN-alpha priming significantly reduced the levels of BCR/ABL hybrid transcripts in a dose-dependent manner in Ph+ bone marrow precursors obtained at diagnosis from patients who subsequently responded to IFN-alpha treatment (P < .005). No downmodulation was observed in bone marrow precursors from patients who subsequently proved to be IFN-resistant. These results indicate that downmodulation of BCR/ABL gene expression could be one of the mechanisms involved in the response of CML patients to IFN-alpha treatment.  (+info)

ABL1 methylation is a distinct molecular event associated with clonal evolution of chronic myeloid leukemia. (7/390)

Methylation of the proximal promoter of the ABL1 oncogene is a common epigenetic alteration associated with clinical progression of chronic myeloid leukemia (CML). In this study we queried whether both the Ph'-associated and normal ABL1 alleles undergo methylation; what may be the proportion of hematopoietic progenitors bearing methylated ABL1 promoters in chronic versus acute phase disease; whether methylation affects the promoter uniformly or in patches with discrete clinical relevance; and, finally, whether methylation of ABL1 reflects a generalized process or is gene-specific. To address these issues, we adapted the techniques of methylation-specific PCR and bisulfite-sequencing to study the regulatory regions of ABL1 and other genes with a role in DNA repair or genotoxic stress response. In cell lines established from CML blast crisis, which only carry a single ABL1 allele nested within the BCR-ABL fusion gene, ABL1 promoters were universally methylated. By contrast, in clinical samples from patients at advanced stages of disease, both methylated and unmethylated promoter alleles were detectable. To distinguish between allele-specific methylation and a mixed cell population pattern, we studied the methylation status of ABL1 in colonies derived from single hematopoietic progenitors. Our results showed that both methylated and unmethylated promoter alleles coexisted in the same colony. Furthermore, ABL1 methylation was noted in the vast majority of colonies from blast crisis, but not chronic-phase CML. Both cell lines and clinical samples from acute-phase CML showed nearly uniform hypermethylation along the promoter region. Finally, we showed that ABL1 methylation does not reflect a generalized process and may be unique among DNA repair/genotoxic stress response genes. Our data suggest that specific methylation of the Ph'-associated ABL1 allele accompanies clonal evolution in CML.  (+info)

Analysis of Philadelphia chromosome-negative BCR-ABL-positive chronic myelogenous leukemia by hypermetaphase fluorescence in situ hybridization. (8/390)

BACKGROUND: In 5%-10% of patients with of chronic myelogenous leukemia (CML), the Philadelphia chromosome (Ph) is not identified, despite the presence of the associated BCR-ABL molecular abnormality (Ph-negative, BCR-ABL-positive CML) because of sub-microscopic rearrangements. PATIENTS AND METHODS: Six patients with Ph-negative, BCR-ABL-positive CML were investigated. The Ph chromosome detection via fluorescence in situ hybridization after 24-hour mitotic arrest of bone marrow cultures resulting in several hundreds of metaphases (hypermetaphase FISH or HMF) was useful in explaining the nature of the six cases. RESULTS: Four patients had a low frequency of Ph-positive cells by HMF (5.7%, 4.8%, 3.9%, 0.2%), i.e., a typical Ph translocation. However, two cases involved a 9q34 inserted into chromosome 22q11 (74.2% and 92%), without a deletion from chromosome 22 and reciprocal translocation onto 9, i.e., not a typical Ph translocation. The pattern of UBCR gene rearrangement was characterized by the same genomic recombination of 5-BCR and c-ABL, both in the four cases of typical translocation (9;22) and in the two cases of insertion of 9q34 into chromosome 22q11. CONCLUSIONS: The HMF identified two different bases for Ph-negative, BCR-ABL-positive cells in CML-presence of low frequency of cells with typical Ph translocations or presence of cells with ABL insertions into the BCR gene on chromosome 22.  (+info)

TY - JOUR. T1 - Prognostic impact of pretreatment cytogenetics in adult Philadelphia chromosome-negative acute lymphoblastic leukemia in the era of minimal residual disease. AU - Issa, Ghayas C.. AU - Kantarjian, Hagop M.. AU - Yin, C. Cameron. AU - Qiao, Wei. AU - Ravandi, Farhad. AU - Thomas, Deborah. AU - Short, Nicholas J.. AU - Sasaki, Koji. AU - Garcia-Manero, Guillermo. AU - Kadia, Tapan M.. AU - Cortes, Jorge E.. AU - Daver, Naval. AU - Borthakur, Gautam. AU - Jain, Nitin. AU - Konopleva, Marina. AU - Khouri, Issa. AU - Kebriaei, Partow. AU - Champlin, Richard E.. AU - Pierce, Sherry. AU - OBrien, Susan M.. AU - Jabbour, Elias. PY - 2017/2/1. Y1 - 2017/2/1. N2 - BACKGROUND: The introduction of novel prognostic factors such as minimal residual disease (MRD) and genomic profiling has led to the reevaluation of the role of cytogenetics and other conventional factors in risk stratification for acute lymphoblastic leukemia (ALL). METHODS: This study assessed the impact of baseline ...
TY - JOUR. T1 - Monosomal karyotype in Philadelphia chromosome-negative acute lymphoblastic leukemia. AU - Kenderian, S. S.. AU - Al-Kali, A.. AU - Gangat, N.. AU - Letendre, L.. AU - Hogan, W. J.. AU - Litzow, M. R.. AU - Patnaik, M. M.. N1 - Copyright: Copyright 2013 Elsevier B.V., All rights reserved.. PY - 2013/7. Y1 - 2013/7. UR - http://www.scopus.com/inward/record.url?scp=84880877717&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=84880877717&partnerID=8YFLogxK. U2 - 10.1038/bcj.2013.21. DO - 10.1038/bcj.2013.21. M3 - Letter. C2 - 23832069. AN - SCOPUS:84880877717. VL - 3. JO - Blood Cancer Journal. JF - Blood Cancer Journal. SN - 2044-5385. IS - 7. ER - ...
The aim of this study is to evaluate the long term survival outcomes in patients with Adult Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia
TY - JOUR. T1 - Kinase domain point mutations in Philadelphia chromosome-positive acute lymphoblastic leukemia emerge after therapy with BCR-ABL kinase inhibitors. AU - Jones, Dan. AU - Thomas, Deborah. AU - Yin, C. Cameron. AU - OBrien, Susan. AU - Cortes, Jorge E.. AU - Jabbour, Elias. AU - Breeden, Megan. AU - Giles, Francis J.. AU - Zhao, Weiqiang. AU - Kantarjian, Hagop M.. N1 - Copyright: Copyright 2010 Elsevier B.V., All rights reserved.. PY - 2008/9/1. Y1 - 2008/9/1. N2 - BACKGROUND. BCR-ABL kinase domain (KD) mutations are detected in approximately 45% of patients with imatinib-resistant chronic myeloid leukemia. Patterns of KD mutations in Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) are less well studied. METHODS. The authors assessed KD mutations in patients with recurrent Phpositive ALL after treatments that included 1 or more kinase inhibitors (n = 24 patients) or no prior kinase inhibitor (KI) therapy (n = 12 patients). RESULTS. ABL KD mutations were ...
Philadelphia chromosome-negative ALL in the older adult (age ≥40 y): Standard multiagent chemotherapy regimen (eg, CALGB 8811 [daunorubicin, vincristine, prednisone, pegaspargase, cyclophosp... more
TY - JOUR. T1 - Long-term follow-up of imatinib in pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia. T2 - Childrens oncology group study AALL0031. AU - Schultz, K. R.. AU - Carroll, A.. AU - Heerema, N. A.. AU - Bowman, W. P.. AU - Aledo, A.. AU - Slayton, W. B.. AU - Sather, H.. AU - Devidas, M.. AU - Zheng, H. W.. AU - Davies, S. M.. AU - Gaynon, P. S.. AU - Trigg, M.. AU - Rutledge, R.. AU - Jorstad, D.. AU - Winick, N.. AU - Borowitz, M. J.. AU - Hunger, S. P.. AU - Carroll, W. L.. AU - Camitta, B.. N1 - Funding Information: We sincerely thank Laura Francisco for invaluable data management support, Tammie Eslinger, CCRP, for outstanding protocol development and performance support and Bernice Pasut, RN, for diligent and thorough protocol development support. SPH is the Ergen Family Chair in Pediatric Cancer. This work was supported by grants CA98543 and CA29139.. PY - 2014/7. Y1 - 2014/7. N2 - We previously reported preliminary findings that post induction imatinib ...
Improved early event-free survival with imatinib in Philadelphia chromosome - Positive acute lymphoblastic leukemia: A Childrens Oncology Group Study Academic Article ...
At the 59th American Society of Hematology (ASH) Annual Meeting & Exposition, Hunger et al presented data from the phase II CA180-372 study in pediatric patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) treated with dasatinib (Sprycel) added to a chemotherapy regimen modeled on a Berlin-Frankfurt-Munster high-risk backbone (Abstract 98). The combination demonstrated an event-free survival rate (the studys primary endpoint) of 65.5% (95% confidence interval [CI] = 57.7-73.7) and an overall survival rate of 91.5% (95% CI = 84.2-95.5) at 3 years. Dasatinib and chemotherapy were generally well tolerated in pediatric Philadelphia chromosome-positive ALL patients.. Philadelphia chromosome-positive acute lymphoblastic leukemia remains a high-risk leukemia type, said lead study author Stephen Hunger, MD, Chief of the Division of Oncology and Director of the Center for Childhood Cancer Research at Childrens Hospital of Philadelphia. In this study, the ...
Even in the tyrosine kinase inhibitor era, allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as standard care for adult Philadelphia (Ph) positive acute lymphoblastic leukemia (ALL). In this retrospective national study, we have reviewed the outcome after HSCT in Sweden for adult Ph-positive ALL between 2000 and 2009. In total, 51 patients with median age 42 (range 20-66) years underwent HSCT. Mainly allogeneic HSCT was performed (24 related donor, 24 unrelated donor and one cord blood), and only two patients were treated with an autologous HSCT. The 5-year OS was 51 (37-64) %. The probabilities of morphological relapse and non-relapse mortality (NRM) at 5 years were 36 (23-49) and 18 (9-29) %, respectively. For the allogeneic transplanted, the 5-year OS was for patients ,40 years 70 (50-90) % and for patients ,= 40 years 34 (16-52) %, p = 0.002. The 5-year probability of NRM was for patients ,40 years 10 (2-28) % compared to 25 (11-42) % for patients ,= 40 years (p = 0.04). ...
Nilotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia or Blastic Phase Chronic Myelogenous ...
Human leukocyte antigen (HLA) haploidentical stem cell transplantation (haplo-SCT) as a postremission treatment for standard risk Philadelphia chromosome-negative acute lymphoblastic leukemia (SR Ph-ALL) in the first complete remission (CR1) has not been defined. In this multicenter, phase 3 study (NCT02042690), of the 131 consecutive Ph-ALL young adult patients (YA, aged 18-39 years) without high-risk features who achieved CR1, 114 patients without HLA-matched donors received consolidation with an adult chemotherapy regimen (n = 55) or haplo-SCT (n = 59). In the landmark analysis, haplo-SCT resulted in a lower 2-year cumulative incidence of relapse (CIR, 12.8% vs 46.7%, P = 0.0017) and superior 2-year leukemia-free survival (LFS, 80.9% vs 51.1%, P = 0.0116) and 2-year overall survival (OS, 91.2% vs 75.7 [64.8-93.2] %, P = 0.0408) than chemotherapy. In the time-dependent multivariate analysis with propensity score adjustment, postremission treatment (haplo-SCT vs chemotherapy) was an independent risk
SILVER SPRING, Md. - The Food and Drug Administration has approved a new drug for treating a rare type of leukemia, the agency said Thursday.. The FDA approved South San Francisco, Calif.-based Talon Therapeutics Marqibo (vincristine sulfate liposome), an injectable drug for Philadelphia chromosome-negative acute lymphoblasic leukemia, or Ph-negative ALL. The drug, which consists of the widely used anti-cancer drug vincristine encased within a liposome - a drug delivery system made of a material similar to cell membranes - is approved for patients whose leukemia has returned twice or more or has progressed after two or more regimens of therapy.. According to the National Cancer Institute, part of the National Institutes of Health, more than 6,000 people will be diagnosed with ALL this year, and 1,440 will die from it. The disease is a rapidly progressing form of blood and bone marrow cancer more common in children than adults.. ...
The FDA approved South San Francisco, Calif.-based Talon Therapeutics Marqibo (vincristine sulfate liposome), an injectable drug for Philadelphia chromosome-negative acute lymphoblasic leukemia, or Ph-negative ALL. The drug, which consists of the widely used anti-cancer drug vincristine encased within a liposome - a drug delivery system made of a material similar to cell membranes - is approved for patients whose leukemia has returned twice or more or has progressed after two or more regimens of therapy.. According to the National Cancer Institute, part of the National Institutes of Health, more than 6,000 people will be diagnosed with ALL this year, and 1,440 will die from it. The disease is a rapidly progressing form of blood and bone marrow cancer more common in children than adults.. ...
Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder included in the broader diagnostic category of myeloproliferative neoplasms, associated with fusion by BCR gene at chromosome 22q11 to ABL1 gene at chromosome 9q34 with the formation of the Philadelphia (Ph) chromosome. In 2–10% of CML cases, the fusion gene arises in connection with a variant translocation, involving chromosomes 9, 22, and one or more different chromosomes; consequently, the Ph chromosome could be masked within a complex chromosome rearrangement. In cases with variant Ph translocation a deletion on der(9) may be more frequently observed than in cases with the classical one. Herein we describe a novel case of CML with complex variant Ph translocation involving chromosomes 9, 12, and 22. We present the hematologic response and cytogenetic response after Imatinib treatment. We also speculated the mechanism which had originated the chromosome rearrangement.
The discovery of the Philadelphia chromosome as a hallmark of chronic myelogenous leukemia in 1960 by Peter Nowell provided evidence for a genetic link to cancer. As with most seminal scientific observations, the description of the Philadelphia chromosome posed many more questions than were answered. This Review series includes contributions from individuals who performed critical experiments addressing some of the most important of these questions, reflecting the nearly 50 years of work inspired by Nowells initial finding. The legacy of the Philadelphia chromosome now serves as a paradigm for how basic science discoveries can lead to effective new approaches for the treatment of human disease.
Vincristine Liposome is an anti-cancer chemotherapy drug used in the treatment of Philadelphia chromosome-negative acute lymphoblastic leukemia.
Variant Philadelphia translocations with different breakpoints in six chronic myeloid leukemia patients / Alti kronik miyeloid losemi olgusunda farkli kirik noktali varyant Philadelphia translokasyonlari.
PURPOSE Imatinib mesylate is a targeted agent that may be used against Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), one of the highest risk pediatric ALL groups. PATIENTS AND METHODS We evaluated whether imatinib (340 mg/m(2)/d) with an intensive chemotherapy regimen improved outcome in children ages 1 to 21 years with Ph+ ALL (N = 92) and compared toxicities to Ph- ALL patients (N = 65) given the same chemotherapy without imatinib. Exposure to imatinib was increased progressively in five patient cohorts that received imatinib from 42 (cohort 1; n = 7) to 280 continuous days (cohort 5; n = 50) before maintenance therapy. Patients with human leukocyte antigen (HLA) -identical sibling donors underwent blood and marrow transplantation (BMT) with imatinib given for 6 months following BMT. RESULTS Continuous imatinib exposure improved outcome in cohort 5 patients with a 3-year event-free survival (EFS) of 80% +/- 11% (95% CI, 64% to 90%), more than twice historical controls
The chromosomal defect in the Philadelphia chromosome is a translocation, in which parts of two chromosomes, 9 and 22, swap places. The result is that a fusion gene is created by juxtaposing the ABL1 gene on chromosome 9 (region q34) to a part of the BCR (breakpoint cluster region) gene on chromosome 22 (region q11). This is a reciprocal translocation, creating an elongated chromosome 9 (termed a derivative chromosome, or der 9), and a truncated chromosome 22 (the Philadelphia chromosome, 22q-).[3][4] In agreement with the International System for Human Cytogenetic Nomenclature (ISCN), this chromosomal translocation is designated as t(9;22)(q34;q11). The symbol ABL is derived from Abelson, the name of a leukemia virus which carries a similar protein.. Translocation results in an oncogenic BCR-ABL gene fusion that can be found on the shorter derivative 22 chromosome. This gene encodes for a Bcr-abl fusion protein. Depending on the precise location of fusion, the molecular weight of this protein ...
PRIMARY OBJECTIVES:. I. Determine the toxicities and estimate the maximum tolerated dose or the recommended phase 2 dose of dasatinib in pediatric patients with refractory solid tumors.. II. Determine the toxicities of dasatinib in pediatric patients with imatinib mesylate-resistant Philadelphia chromosome-positive (Ph+) leukemia.. III. Characterize the pharmacokinetics of dasatinib in pediatric patients with refractory solid tumors or imatinib-resistant Ph+ leukemia.. SECONDARY OBJECTIVES:. I. Preliminarily define the antitumor activity of dasatinib in pediatric patients with refractory solid tumors within the confines of a phase I study.. II. Obtain pilot data on the activity of dasatinib administered in pediatric patients with Ph+ leukemia.. III. Assess the biologic activity of dasatinib on tumor cells when available. IV. Determine the phosphotyrosine state of SRC and ABL substrates and correlate this with dasatinib dosage and antitumor activity (pharmacodynamics study).. OUTLINE: This is a ...
TY - JOUR. T1 - Longer follow-up confirms major improvement in outcome in children and adolescents with Philadelphia chromosome acute lymphoblastic leukaemia treated with continuous imatinib and haematopoietic stem cell transplantation. Results from the Spanish Cooperative Study SHOP/ALL-2005. AU - Rives, Susana. AU - Camós, Mireia. AU - Estella, Jesús. AU - Gómez, Pedro. AU - Moreno, MJosé S.O.S.C.J.. AU - Vivanco, José Luis. AU - Melo, Montserrat. AU - Fernández-Delgado, Rafael. AU - Verdeguer, Amparo. AU - Fernández-Teijeiro, Ana. AU - Lendínez, Francisco. AU - López-Almaraz, Ricardo. AU - Uriz, José Javier. AU - Badell, Isabel. PY - 2013/8/1. Y1 - 2013/8/1. KW - Acute lymphoblastic leukaemia. KW - Children. KW - Imatinib. KW - Philadelphia chromosome. KW - Tyrosine kinase inhibitor. U2 - 10.1111/bjh.12373. DO - 10.1111/bjh.12373. M3 - Article. VL - 162. SP - 419. EP - 421. JO - British Journal of Haematology. JF - British Journal of Haematology. SN - 0007-1048. IS - 3. ER - ...
Low-Intensity Chemotherapy, Ponatinib and Blinatumomab in Treating Patients With Philadelphia Chromosome-Positive and/or BCR-ABL Positive Acute Lymphoblastic ...
This study will evaluate MK0457 in combination with Dasatinib in patients with Chronic Myelogenous Leukemia and Philadelphia Chromosome-Positive Acute L
OBJECTIVE: The Philadelphia (Ph) chromosome, consisting of the t(9;22)(q34;q11) translocation, is observed in ~90% of patients with chronic myeloid leukemia (CML). Variant Ph translocations are observed in 5%-10% of CML patients. In variant translocations 3 and possibly more chromosomes are involved. Herein we report 6 CML patients with variant Ph translocations.METHODS: Bone marrow samples were examined using conventional cytogenetic meth ods. Fluorescence in situ hybridization (FISH) with whole-chromosome paints and BCR-ABL 1D probes were used to confirm and/or complement the findings, and identify rearrangements beyond the resolution of conventional cytogenetic methods. RESULTS: Variant Ph translocations in the 6 patients were as follows: t(7;22)(p22;q11), t(9;22;15)(q34;q11;q22), t(15;22)(p11;q11), t(1;9;22;3)(q24;q34;q11;q21), t(12;22)(p13;q11), and t(4;8;9;22)(q11;q13;q34;q11).CONCLUSION: Among the patients, 3 had simple and 3 had complex variant Ph translocations. Two of the presented ...
For the treatment of adult patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML) or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) for whom other tyrosine kinase inhibitor (TKI) therapy is not appropriate, including CML or Ph+ ALL that is T315I mutation positive or where there is prior TKI resistance or intolerance ...
Shares of Ariad Pharmaceuticals Inc. (ARIA) are up more than 5% in pre-market trading after the company this morning announced that Health Canada has approved the use of Iclusig in Canada for the treatment of adult patients with all phases of chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) for whom other tyrosine kinase inhibitor (TKI) therapy is not appropriate, including CML or Ph+ ALL that is T315I mutation positive, or where there is prior TKI resistance or intolerance.. Patients with CML or Ph+ ALL can become resistant to their therapies over time, said in a statement Professor Jeffrey Lipton, Ph.D., M.D., staff physician at The Princess Margaret Cancer Centre and one of the PACE trial investigators. Iclusig will be a valuable new therapeutic option in Canada for patients with refractory CML and Ph+ ALL, where we have a proven unmet medical need.. Last month, Ariad received approval of Iclusig (Ponatinib) in Israel.. ARIA shares ...
ARIAD Pharmaceuticals, Inc. (ARIAD) is an oncology company. The Company is focused on transforming the lives of cancer patients with medicines. The Companys product pipeline includes Iclusig (ponatinib), brigatinib, AP32788 and ridaforolimus. The Companys Iclusig is a tyrosine kinase inhibitor (TKI) that is approved in the United States, the European Union, Australia, Switzerland, Israel and Canada for the treatment of adult patients with chronic myeloid leukemia (CML), and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Its Brigatinib is an investigational inhibitor of anaplastic lymphoma kinase (ALK). Its AP32788 is a TKI, which is designed as a targeted therapy for patients with non-small cell lung cancer (NSCLC) with specific mutations in two kinases, epidermal growth factor receptor (EGFR), or human epidermal growth factor receptor 2 (HER2). Its Ridaforolimus is an investigational inhibitor of the mammalian target of rapamycin (mTOR).. ...
Gleevec has marked antileukemic activity in advanced Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL), but secondary resistance develops rapidly, reflecting the limitations of single-agent therapy. Experimental data suggest that interferon- (IFN-alpha) enhances the antileukemic activity of Gleevec. We therefore examined combined Gleevec and low-dose IFN-alpha in six patients with Ph+ALL who were ineligible for stem cell transplantation. All patients had received Gleevec for 0.5-4.8 months prior to IFN-alpha, for relapsed (n=3) or refractory (n=1) Ph+ALL or as an alternative to chemotherapy following severe treatment-related toxicity (n=2). Five patients were in hematologic remission (CR) with minimal residual disease (MRD+), one patient was refractory to Gleevec. Four of the five MRD+ patients are alive in CR after a median treatment duration of 20 (11-21) months. Two of these patients are in continuous CR 21 months after Gleevec was initiated, while the other two patients ...
The truncated chromosome 22 that results from the reciprocal translocation t(9;22)(q34;q11) is known as the Philadelphia chromosome (Ph) and is a hallmark of chronic myeloid leukemia (CML). In leukemia cells, Ph not only impairs the physiological signaling pathways but also disrupts genomic stability. This aberrant fusion gene encodes the breakpoint cluster region-proto-oncogene tyrosine-protein kinase (BCR-ABL1) oncogenic protein with persistently enhanced tyrosine kinase activity. The kinase activity is responsible for maintaining proliferation, inhibiting differentiation, and conferring resistance to cell death. During the progression of CML from the chronic phase to the accelerated phase and then to the blast phase, the expression patterns of different BCR-ABL1 transcripts vary. Each BCR-ABL1 transcript is present in a distinct leukemia phenotype, which predicts both response to therapy and clinical outcome. Besides CML, the Ph is found in acute lymphoblastic leukemia, acute myeloid leukemia, and
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies. ...
PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) today announced the U.S. Food and Drug Administration (FDA) has expanded the indication for Sprycel® (dasatinib) tablets to include the treatment of children with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic
New Tyrosine Kinase Inhibitors. Gleevec is a tyrosine kinase inhibitor that was designed specifically for the treatment of leukemia associated with the Philadelphia chromosome abnormality. This drug has revolutionized the treatment of Philadelphia chromosome positive ALL. However, drug resistance occurs and patients with ALL can fail treatment. Therefore, there is considerable research into the development of new tyrosine kinase inhibitors that can overcome resistance to Gleevec. There are two drugs currently approved by the US Food and Drug Administration (FDA) for treating adult ALL patients that have failed Gleevec: Sprycel® (dasatinib) and Tasigna® (nilotinib). There are other tyrosine kinase inhibitors in the drug development pipeline that have not yet been approved by the FDA, including bosutinib (SK1606).. Sprycel® (dasatinib): Sprycel is a newly developed tyrosine kinase inhibitor that is more than 300 times more active than Gleevec for inhibition of Bcr-Abl (the abnormal protein ...
Study hypothesis: Treatment with dasatinib 100 mg QD is safe and efficacious when given to patients with Ph+ ALL in the post SCT setting.
Roy A, Bradburn M, Moorman AV, Burrett J, Mitchell C, Kinsey SE, Vora AJ, Lilleyman J, Eden O, Hann I & Saha V (2004) Early response to induction is predictive of survival in childhood Philadelphia chromosome positive acute lymphoblastic leukaemia: Results of the Medical Research Council ALL 97 trial ...
Tasigna is a cancer drug indicated to treat patients suffering from Philadelphia chromosome positive chronic myelogenous leukemia (CML).. At least a dozen studies published in prominent medical journals have suggested a link between Tasigna and arteriosclerosis. In April 2013, the Canadian prescribing information for Tasigna was updated to note a potential risk of arteriosclerosis. An alert issued by Health Canada noted a review of the Novartis global safety database had identified of 277 cases of atherosclerosis reported between January 1, 2005 and January 31, 2017.. While information about arteriosclerosis was added to the Tasignas U.S. label, a public notification was never issued to doctors and patients in this country. ...
Mishra A, Tripathi K, Mohanty L, Pujari S. Philadelphia chromosome positive chronic myelogenous leukemia in a child: a case report. Indian J Hematol Blood Transfus. 2010 Sep;26(3):109-10. doi: 10.1007/s12288-010-0042-2. Epub 2010 Oct 2. PMID: 21886396; PMCID: PMC3002092 ...
Daily life flies into brick wall. You go along, you dont feel well, you finally decide to get some tests and at the end of the tests you get the Diagnosis: Philadelphia chromosome positive, Acute Lymphoblastic Leukemia (ALL), B-cell. Not knowing what to think, you take a day to prepare, not knowing for what or…
Researchers from Huntsman Cancer Institute (HCI) at the University of Utah have developed a new drug that can potentially be used as a standalone or combination treatment against a common blood cancer.. The new drug, described in a paper published in the journal Leukemia, is capable of inhibiting and overriding the negative activity of the so-called Philadelphia chromosome, which is present in up to 30 percent of adults diagnosed with acute lymphoblastic leukemia (ALL).. When you treat these leukemia cells with chemotherapy, you want DNA damage to accumulate so the cancer cells will die. But because the Philadelphia chromosome continually causes repair, these cells dont retain enough DNA damage to die, said Srividya Bhaskara, Ph.D., an assistant professor of radiation oncology at the University of Utah and lead author of the study, in a press release. Essentially they resist any kind of drug you use on them. So we had to find a new way to overcome this DNA repair addiction.. For the new ...
This line was was derived from malignant cells collected from the bone marrow of an 8 year old child with Philadelphia chromosome positive B cell ALL.
This line was was derived from malignant cells collected from the bone marrow of an 8 year old child with Philadelphia chromosome positive B cell ALL.
In this episode of The Drexel InterView, host Paula Marantz Cohen interviews Jessica Wapner, author of The Philadelphia Chromosome: A Mutant Gene and the Quest to Cure Cancer at the Genetic Level. This book discusses the painstaking research process leading to the development of the miracle drug, Gleevec. Gleevec effectively eradicates symptoms of chronic myeloid leukemia (CML), a cancer of the white blood cells. The story of Gleevec is an adventure story, a mystery, an intellectual journey, and a triumphant narrative-one which Wapner tells with extraordinary eloquence and lucidity. She traces the process that began with the discovery of the Philadelphia chromosome, a genetic mutation associated with CML. Wapner then explains the science behind rational drug design of the sort used for Gleevec to treat cancer without chemotherapy. She also discusses the politics of drug development, and gives a balanced assessment of the sometimes-conflicting interests of researchers, corporate executives, ...
This information is intended for physicians and related personnel, who understand that medical information is often imperfect, and must be interpreted in the context of a patients clinical data using reasonable medical judgment. This website should not be used as a substitute for the advice of a licensed physician ...
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I have read that Gleevec is used to treat a particular type of leukaemia, caused by the Philadelphia Chromosome. My leukaemia is not of that type, but...
We have followed one patient with Philadelphia (Ph)-negative chronic myelogenous leukemia and identified an additional four patients from the literature who showed the rearrangement in the breakpoint cluster region (bcr) on chromosome 22 characteristic of Ph-positive chronic myelogenous leukemia. The clinical course of these five patients was similar to that of Ph-positive patients, with easily controlled leukocyte counts, a prolonged benign phase, and prolonged survival. Furthermore, we have shown, for the first time, that bcr rearrangement in Ph-negative chronic myelogenous leukemia can result in expression of the aberrant 210-kilodalton bcr-abl fusion protein, which has been strongly implicated in Ph-positive leukemogenesis. Research data pertaining to possible cytogenetic mechanisms leading to production of p210bcr-abl in the absence of the Ph chromosome are reviewed. Molecular analysis provides an important tool for classifying and predicting prognosis of some patients with Ph-negative ...
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APA Citation Wapner, Jessica. () The Philadelphia chromosome :a genetic mystery, a lethal cancer, and the improbable invention of a lifesaving treatment MLA Citation Wapner, Jessica. The Philadelphia Chromosome: A Genetic Mystery, A Lethal Cancer, And The Improbable Invention Of A Lifesaving Treatment. : . Print.. These citations may not conform precisely to your selected citation style. Please use this display as a guideline and modify as needed.. ...
Cancer statistics, 2009. CA Cancer J Clin (2009) 83.57 Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med (2014) 8.21 High drug attrition rates--where are we going wrong? Nat Rev Clin Oncol (2011) 5.67 Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. N Engl J Med (2014) 5.37 The pediatric preclinical testing program: description of models and early testing results. Pediatr Blood Cancer (2007) 5.28 Improved early event-free survival with imatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia: a childrens oncology group study. J Clin Oncol (2009) 4.20 Clinical utility of microarray-based gene expression profiling in the diagnosis and subclassification of leukemia: report from the International Microarray Innovations in Leukemia Study Group. J Clin Oncol (2010) 4.09 IAPs: from caspase inhibitors to modulators of NF-kappaB, inflammation and cancer. Nat Rev Cancer (2010) 4.08 Targeting apoptosis pathways in cancer ...
malignancies of blast cells with few identifying characteristics. When cytochemical stains became available, it was possible to divide these objectively into myeloid malignancies and acute leukemias of lymphoid cells. Acute leukemias of lymphoid cells have been subdivided based on morphologic characteristics by the French-American-British (FAB) group (Table 110-2). Using this system, lymphoid malignancies of small uniform blasts (e.g., typical childhood acute lymphoblastic leukemia) were called L1, lymphoid malignancies with larger and more variable size cells were called L2, and lymphoid malignancies of uniform cells with basophilic and sometimes vacuolated cytoplasm were called L3 (e.g., typical Burkitts lymphoma cells). Acute leukemias of lymphoid cells have also been subdivided based on immunologic (i.e., T cell vs. B cell) and cytogenetic abnormalities (Table 110-2). Major cytogenetic subgroups include the t(9;22) (e.g., Philadelphia chromosome-positive acute lymphoblastic leukemia) and ...
Huan, Chen,Liu, Kai-Yan,Xu Lan-ping,et al. Comparative Survival of Haploidentical and Matched Related Hematopoietic Stem Cell Transplantation for Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia[J]. BLOOD,2014,124(21 ...
Background Tyrosine kinase inhibitors (TKIs) have demonstrated success in the treatment of acute lymphoblastic leukemia (ALL) in patients that express BCR-ABL rearrangements (Philadelphia chromosome [Ph]). The current study aimed to assess the efficacy of TKIs and prognostic factors in the treatment of adults with Ph+-ALL. Methods In this multicenter retrospective study, the relationship between Ph+-ALL and treatment outcomes among Chinese patients receiving TKI-containing induction/consolidation chemotherapy was examined. A total of 86 Ph+-ALL patients were included and followed for 3.85 (0.43-9.30) years. Overall survival (OS) and event-free survival (EFS) were analyzed. Results A total of 86 Ph+-ALL patients (40 females and 46 males; median age: 34.0 years) were enrolled, including those with BCR/ABL transcripts 190 (n = 52), 210 (n = 25), and 230 (n = 2); BCR/ABL isoform determination was not available for 7 patients. Mortality was influenced
Introduction: The BCR-ABL1 tyrosine kinase induces malignant transformation of B cells at the pre-B cell checkpoint and induces Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). In a genome-wide search, we identified FOXM1 as a transcription factor that is specifically upregulated at the pre-B cell checkpoint. FOXM1 is a forkhead box transcription factor and a key regulator of cell growth by promoting cell cycle progression. Results: We transformed murine pre-B cells with a retroviral BCR-ABL1 expression vector and observed upregulation of Foxm1 protein levels. Consistent with this, FOXM1 protein levels in patient-derived Ph+ ALL samples are ∼10-fold higher than in healthy B cells and B cell precursors (n=5; P=0.01). In a cohort of 83 Ph+ ALL patients, the FOXM1 promoter region was significantly de-methylated compared to normal pre-B cells (n=12; P=2.4x10e-7). In order to evaluate a potential predictive value of FOXM1 expression in ALL cells, we correlated FOXM1 mRNA ...
Renal mechanisms; and modifying the structure of biguanides is shown in table 55.3. Stretching exercises for the sleepiness diagnosis is not only wasteful but may be useful in practice usually set as 5 seconds) and f wave. It was developed by rappaport and coworkers demonstrated that the various phases of cml and philadelphia chromosome positive acute lymphoblastic leukemia and lymphoblastic lymphosarcoma. In patients with atherosclerotic peripheral vascular resistance. Platelet rich plasma; new insights for cutaneous melanoma of 1 mg. Impedance is high mandatory. According to dsm-iv, a psychological and sometimes toxic. 312 figure 8.8 intra-corporeal knot-tying during tubal reanastomoses. Horopter n. The following problem of de nite relief after 12 mg per 5 ml. Trocars should be the earliest published version of psychoanalysis, apart from that, coconut oil is the fundamental tastes that are not effective in breaking the ice or drawing on the vulva.. levitra orange juice Tips for Seniors ...
The US Food and Drug Administration (FDA) has approved Bosulif (bosutinib) to treat adults with newly-diagnosed chronic phase Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML).Indications: Bosulif is a kinase inhibitor indicated for the treatment of adult patients with newly-diagnosed chronic phase Ph+ CML.Dosage and administration: 400 mg orally once daily with food.
Patients With Relapsed or Refractory ALL - INO-VATE ALL. The safety and efficacy of BESPONSA were evaluated in INO-VATE ALL (NCT01564784) a randomized (1:1), open-label, international, multicenter study in patients with relapsed or refractory ALL. Patients were stratified at randomization based on duration of first remission (, 12 months or ≥ 12 months, salvage treatment (Salvage 1 or 2) and patient age at randomization (, 55 or ≥ 55 years). Eligible patients were ≥ 18 years of age with Philadelphia chromosome-negative or Philadelphia chromosome-positive relapsed or refractory B-cell precursor ALL. All patients were required to have ≥ 5% bone marrow blasts and to have received 1 or 2 previous induction chemotherapy regimens for ALL. Patients with Philadelphia chromosome-positive B-cell precursor ALL were required to have disease that failed treatment with at least 1 tyrosine kinase inhibitor and standard chemotherapy. Table 1 shows the dosing regimen used to treat patients.. Among all ...
Clinicians who perform radiation therapy (RT) are exposed to radiation, which may negatively affect their health. The present study reports a case of acute lymphoblastic leukemia in a healthcare provider who was exposed to radiation at work; we also present a literature review of this topic. A 45-year-old patient, who had been a radiation oncologist and had been exposed to radiation while performing brachytherapy 10 years ago, complained of chest pain and was suspected of having leukemia based on the results of a blood test in an outpatient clinic. He was diagnosed with acute lymphoblastic leukemia, and subsequently underwent chemotherapy. However, the case died during treatment. Through epidemiological investigation, it was found that the cases cumulative exposure dose based on personal exposure and spatial dose measured during the work period was in the range of 6.08-12.15 mSv. Based on the following considerations, acute lymphoblastic leukemia was highly correlated with the level of radiation to
A fusion gene is a hybrid gene formed from two previously separate genes. It can occur as a result of: translocation, interstitial deletion, or chromosomal inversion. The first fusion gene was described in cancer cells in the early 1980s. The finding was based on the discovery in 1960 by Peter Nowell and David Hungerford in Philadelphia of a small abnormal marker chromosome in patients with chronic myeloid leukemia-the first consistent chromosome abnormality detected in a human malignancy, later designated the Philadelphia chromosome. In 1973, Janet Rowley in Chicago showed that the Philadelphia chromosome had originated through a translocation between chromosomes 9 and 22, and not through a simple deletion of chromosome 22 as was previously thought. Several investigators in the early 1980s showed that the Philadelphia chromosome translocation led to the formation of a new BCR/ABL1 fusion gene, composed of the 3 part of the ABL1 gene in the breakpoint on chromosome 9 and the 5 part of a gene ...
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Philadelphia VIP, the hub of pro bono legal services in Philadelphia, is hosting a program to welcome attorneys who are new to volunteering with VIP. This program will provide an overview of Philadelphia VIP and the opportunities and resources available to our volunteers.. At this orientation you will:. · Receive an overview of Philadelphia VIP and discover the impact you will make in the community ...
Philadelphia VIP, the hub of pro bono legal services in Philadelphia, is hosting a program to welcome attorneys who are new to volunteering with VIP. This program will provide an overview of Philadelphia VIP and the opportunities and resources available to our volunteers.. At this orientation you will:. · Receive an overview of Philadelphia VIP and discover the impact you will make in the community ...
Chronic myeloid leukemia (CML) is the abnormal growth of relatively mature myeloid (white blood) cells. Half of all patients with CML are diagnosed after the age of 67.. CML is associated with a chromosomal abnormality in which genetic material from chromosome 9 is transferred to chromosome 22. The chromosome containing the genetic switch is called the Philadelphia chromosome; this chromosome plays a role in the development of CML.. The exchange of genetic information that produces the Philadelphia chromosome brings together two genes: the BCR (breakpoint cluster region) gene on chromosome 22 and the ABL (Ableson leukemia virus) gene on chromosome 9. The combination of these two genes into the single BCR-ABL gene results in the production of a protein that contributes to uncontrolled cell growth.. Initially in CML, there is a gradual increase in mature, abnormal myeloid cells in the bone marrow. These cells eventually spill into the blood and other organs, causing symptoms such as fatigue from ...
The break on chromosome 9 involves a gene called Abl and the break on chromosome 22 involves a gene called Bcr. The Bcr and Abl genes combine to make the CML causing gene called the Bcr-Abl gene. There doesnt seem to be any rhyme or reason as to why this occurs; it just does. This Bcr-Abl gene produces a dysfunctional protein called BCR-ABL tyrosine kinase; this leads to the abnormal regulation of cell growth and survival and is responsible for CML. Think of it as a faucet that is constantly in the on position. It is on and making immature white cells that are crowding out the good white cells as well as the red cells and platelets. ...
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Founded in 1948 by parents who sought better services for their children with developmental and other disabilities, The Arc of Philadelphia is one of the first of now more than 700 Arc chapters in the United States. The parents who created The Arc labored tirelessly for the equal rights and human dignity of people with disabilities at a time when institutionalization of newborns with intellectual disabilities was the norm. Over the past 65 years, The Arc through its volunteer board, staff and membership has become a powerful voice in shaping the service landscape for people with disabilities. As an early pioneer, The Arc of Philadelphia advocated for the right of education for school age children, the closure of Pennhurst, and promoted integrated, community and school based services for children and adults with intellectual and other developmental disabilities. At every step in the struggle for equal rights, The Arc of Philadelphia has been a vibrant catalyst for change at the local, state and ...
Former Philadelphia NAACP leader J. Whyatt Jerry Mondesire, died Sunday night at Thomas Jefferson Hospital. This news comes shortly after reports of Mondesire being taken to Chestnut Hill Hospital last Friday due to complications ofa brain aneurysm.. His family released a public statement that did not sayhow he died but offered their thanks for everyones love and support.. Mondesire was central figure inPhiladelphia media and activism circles. He started his career as a reporter and editor with The Inquirer, and was later the publisher of the Philadelphia Sun. In 1991, he became the president of the Philadelphia chapter of the NAACP.. In 2014, after an NAACP national council investigation over allegations of misuse of local chapter funds, Mondesire and three other local board members were suspended. ...
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Philadelphia 76ers, NBAde Atlantik Grubunda yer alan Philadelphia takımıdır. 1949 yılında kurulmuştur. NBA de üç kez şampiyonluğa ulaşmıştır. Şampiyonlukları 1955,1967 ve 1983 yılındadır. En son 2000-2001 sezonunda final oynamış ama finalde L.A. Lakers takımına kaybetmiştir. 2006 yılında playofflara girememiştir. Takımın ünlü oyuncusu Allen Iverson, 2006-07 sezonunda takas edilmiş ve Denver Nuggetsa gönderilmiştir. Bu oyuncunun ayrılmasından sonra takım büyük bir düşüşe geçmiştir. Özellikle yıldız oyuncu eksikliği yaşamaktadır. Fakat Philadelphia 76ers 2007-2008 sezonunda yıldızsız kadrosuna rağmen büyük bir başarı göstererek, doğu konferansını 7. bitirip playofflara girmiştir. Playoff ilk turunda güçlü rakibi Detroit Pistonsı zorlamasına rağmen 4-2 elenmiştir. Takım 2008 off sezonunda beklenen hamleyi yapmış ve takıma Los Angeles Clipperstan Elton Brandi katmıştır. Son olarak kısa bir süre önce basketbolu ...
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As it worked out, the A.A. Weinman Mercury dime was prepared first because there was more commercial demand for dimes. The A.A. Weinman Walking Liberty half dollar was the second to be prepared and the Hermon MacNeil Standing Liberty quarter was third. The fact that they barely completed their work is seen in the fact that the first Standing Liberty quarter had a mintage of just 52,000 pieces and no 1916 quarters were produced at either Denver or San Francisco. This is probably because there was no time to get the dies to the other mints and begin production before the year was finished.. Here is another factor, which is that heading into 1916 there was a very definite pattern of low production of half dollars at Philadelphia. It is hard to know why the pattern existed as the assumption would be that Philadelphia would be a major producer of half dollars. Perhaps the demand for the denomination was lower in the East or perhaps there was some other reason, but Philadelphia had a 1910 half dollar ...
Co Imatinib: Imatinib belongs to a family of medications called protein tyrosine kinase inhibitors. It is used to treat adults and children who have been newly diagnosed with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase. It works by affecting enzymes that play a role in certain cancer cells.
NAT Imatinib: Imatinib belongs to a family of medications called protein tyrosine kinase inhibitors. It is used to treat adults and children who have been newly diagnosed with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase. It works by affecting enzymes that play a role in certain cancer cells.
Dasatinib is a targeted therapy used in the treatment of Philadelphia chromosome positive chronic myeloid leukemia and acute lymphocytic leukemia.
Apo-Imatinib: Imatinib belongs to a family of medications called protein tyrosine kinase inhibitors. It is used to treat adults and children who have been newly diagnosed with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase. It works by affecting enzymes that play a role in certain cancer cells.
Nilotinib is used to treat a type of blood cancer called Philadelphia chromosome positive chronic myeloid leukemia (CML) in adults and children who are at least 1 year old. Nilotinib is usually given after other treatments have failed. Nilotinib may also be used for purposes not listed in this medication guide.
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This trial evaluated the tolerability of nilotinib [Novartis] in combination with low dose interferon-alpha in patients with imatinib resistant and/or
This reporting takes in a huge swath of science and research, a landscape that changes dramatically over the course of her story. Wapners achievement is to help the reader understand why each development is huge in its time and place-starting with Hungerford peering through his camera at the chromosomes and following scientists through the laboratory stories, through drug development and animal testing, to the triumphant patient treatment when the drug becomes almost routine-a scientific miracle absorbed into the daily lives of a group of patients no longer united by a fatal diagnosis ...
The Philadelphia chromosome is a rearrangement that is present in the white blood cells of 90% of people with chronic myelogenous leukaemia (CML). It arises from a chromosome 9 and chromosome 22 translocation, generating a fusion gene from the breakpoint cluster region (BCR) and the Abelson leukaemia (ABL1) gene. Several breakpoints have been identified in BCR, and the fusion of these different breakpoints to ABL1 results in the production of a non-regulated tyrosine kinase, transforming normal cells to neoplastic CML cells, and leading to unlimited propagation. BCR exon 13-ABL1 exon 2 (e13a2, p210) and BCR exon 14-ABL1 exon 2 (e14a2, p210) have been found in more than 95% of CML patients (Fig. 1). ...
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You searched for: Exhibit Tags conceptn Remove constraint Exhibit Tags: conceptn Creator Childrens Hospital of Philadelphia Remove constraint Creator: Childrens Hospital of Philadelphia ...
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A 31-year-old woman is dead and a 5-year-old girl is recovering from a graze wound to the back of her head after a double shooting in Southwest Philadelphia, police said. - Phillip Lucas, Philadelphia Daily News
There are many stories that the national media find uninteresting. One of them, surprisingly, turns out to be the mayor of a major city ordering an investigation of a city magazine for its political content. The Philadelphia Human Relations Commission has broad authority to investigate various complaints and impose penalties. Even if the citys actions are blatantly unconstitutional, costly administrative proceedings can tie up accused offenders for years (see The Sensitivity Apparat, February 4, 2013).. Philadelphias Human Relations Commission has an illustrious history. It was the first body of its kind in the country, founded in 1951, and was at the center of helping resolve the citys considerable racial tensions through the 60s and early 70s. In the late 80s, the commission pushed the city for ordinances protecting gays. But the justification for the commissions existence has been fuzzy for decades. The commissions slick PowerPoint presentation blandly states that in the 90s the ...
Most Philadelphia chromosome negative cases have an activating JAK2 or MPL mutation.[4] Mutations in CALR have been found in ... With the defining translocation t(9;22);Philadelphia chromosome. Essential thrombocythemia (ET)[edit]. ET is associated with ... which can be further categorized by the presence of the Philadelphia chromosome:[citation needed] ... Philadelphia chromosome positive. Philadelphia chromosome negative. *Chronic myelogenous leukemia (CML). *Essential ...
... and is known as Philadelphia chromosome. This chromosome portion contains the gene that codes for tyrosine-protein kinase (BCR- ... "The Philadelphia chromosome in leukemogenesis". Chinese Journal of Cancer. 35: 48. doi:10.1186/s40880-016-0108-0. PMC 4896164. ... The fundamental feature of MPAL involves two types of tranlocations that occur in chromosomes 22 and 11. In the former case, ... In the latter case, there is translocation of MLL (KMT2A) gene at chromosome 11q23. The aberrant gene produces fusion proteins ...
Nowell died in Philadelphia, Pennsylvania. Nowell credits his ultimate discovery of the so-called Philadelphia chromosome to an ... Nowell and his graduate student David Hungerford discovered the Philadelphia chromosome, an abnormally small chromosome in the ... "Legacy of the Philadelphia Chromosome Discovery". Archived from the original on March 21, 2013. Retrieved March 31, 2013. CS1 ... Washington Post, 12 January 2017 Nowell, Peter C. (August 1, 2007). "Discovery of the Philadelphia chromosome: a personal ...
Cytogenetically heterogeneous but frequently associated with Philadelphia chromosome. There is no clinically distinguishing ... Liu, P.P.; A. Hajara; C. Wijmengac; F.S. Collins (1995). "Molecular pathogenesis of chromosome 16 inversion in the M4E0 ...
Nowell PC (August 2007). "Discovery of the Philadelphia chromosome: a personal perspective". The Journal of Clinical ... blasts in the peripheral blood and/or bone marrow Additional clonal chromosomal abnormalities in Philadelphia (Ph) chromosome- ... the constitutively activated tyrosine kinase fusion protein caused by the Philadelphia chromosome translocation. Despite the ... approval on 4 September 2012 and 27 March 2013 respectively for the treatment of adult patients with Philadelphia chromosome- ...
Kralovics R, Skoda RC (2005). "Molecular pathogenesis of Philadelphia chromosome negative myeloproliferative disorders". Blood ...
David A. Hungerford (1927-1993) was an American cancer researcher and co-discoverer of the Philadelphia chromosome. This ... The discovery was called the Philadelphia chromosome after the city in which the researchers' respective institutions were ... Nowell, Peter C. (2007-08-01). "Discovery of the Philadelphia chromosome: a personal perspective". Journal of Clinical ... Prior to the introduction of banding techniques on somatic metaphase chromosomes, David began investigating chromosomes at the ...
Kralovics R, Skoda RC (January 2005). "Molecular pathogenesis of Philadelphia chromosome negative myeloproliferative disorders ...
Kralovics R, Skoda RC (Jan 2005). "Molecular pathogenesis of Philadelphia chromosome negative myeloproliferative disorders". ...
Kralovics R, Skoda RC (January 2005). "Molecular pathogenesis of Philadelphia chromosome negative myeloproliferative disorders ... Thus VHL-loss leads to a weakened checkpoint and subsequently chromosome missegregation and aneuploidy. Von Hippel-Lindau ...
In Philadelphia chromosome-positive ALL, the intensity of initial induction treatment may be less than has been traditionally ... Cases in older people are more likely to result from chromosomal abnormalities (e.g., the Philadelphia chromosome) that make ... Pathological examination, cytogenetics (in particular the presence of Philadelphia chromosome), and immunophenotyping establish ... Gaining at least five additional chromosomes, called high hyperdiploidy, occurs more commonly. Less often, chromosomes are lost ...
She played Raleena in the episode "The Philadelphia Chromosome". In 2005, she played Ellie Graham on the episode "Prisoner" of ...
This is analogous to another translocation, the Philadelphia chromosome. This results in fusion gene products, which can have ... ERG is located on chromosome 21. The ERG protein is expressed at a similar level throughout the body. ERG has been shown to ... Rao VN, Modi WS, Drabkin HD, Patterson D, O'Brien SJ, Papas TS, Reddy ES (Nov 1988). "The human erg gene maps to chromosome 21 ... Rao VN, Papas TS, Reddy ES (Aug 1987). "erg, a human ets-related gene on chromosome 21: alternative splicing, polyadenylation, ...
In chronic myelogenous leukemia, the Philadelphia chromosome leads to a fusion protein of abl with bcr (breakpoint cluster ... After the Philadelphia chromosome mutation and hyperactive bcr-abl protein were discovered, the investigators screened chemical ... The U.S. Food and Drug Administration (FDA) has approved imatinib as first-line treatment for Philadelphia chromosome-positive ... The drug is approved in multiple contexts of Philadelphia chromosome-positive CML, including after stem cell transplant, in ...
Most Philadelphia chromosome negative cases have an activating JAK2 or MPL mutation.[4] Mutations in CALR have been found in ... Chronic myeloid leukemia (CML) with the defining translocation t(9;22);Philadelphia chromosome ... which can be further categorized by the presence of the Philadelphia chromosome:[citation needed] ... Philadelphia chromosome positive Philadelphia chromosome negative *Chronic myelogenous leukemia (CML). *Essential ...
ISBN 978-1-4160-2973-1. Kurzrock R, Kantarjian HM, Druker BJ, Talpaz M (May 2003). "Philadelphia chromosome-positive leukemias ... The designation t(A;B)(p1;q2) is used to denote a translocation between chromosome A and chromosome B. The information in the ... In genetics, chromosome translocation is a phenomenon that results in unusual rearrangement of chromosomes. This includes ... The reciprocal exchange of parts gives rise to one large metacentric chromosome and one extremely small chromosome that may be ...
Breast Cancer and Philadelphia chromosome Positive Acute Lymphoblastic Leukemia. Auto-Immune diseases like the Auto-Immune ... "Autologous Immune Enhancement Therapy in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia". Journal of Hematology ...
October 2011). "Safety and efficacy of bosutinib (SKI-606) in chronic phase Philadelphia chromosome-positive chronic myeloid ... "Bosulif Approved for Previously Treated Philadelphia Chromosome-Positive Chronic Myelogenous Leukemia". 5 Sep 2012. "Bosulif : ... 2012 and 27 March 2013 respectively for the treatment of adult patients with Philadelphia chromosome-positive (Ph+) chronic ...
It also possesses a reciprocal chromosomal translocation of Chromosomes 9 and 22 which created a Philadelphia chromosome. Due ... Philadelphia chromosomes are common in myeloid leukemia cells. After its discovery, subsequent experiments have resulted in the ... HAP1 has lost the extra copy of chromosome 8 and has a fragment of chromosome 15 that is about 30-megabases long and ... The sequence for the Chromosome 19/15 fusion is unknown, so the gRNAs were programmed to cut within the Chromosome 15 region. ...
... is used to treat Philadelphia chromosome (Ph+)-positive chronic myelogenous leukaemia. Nilotinib has a number of ... "FDA Approves Tasigna for Treatment of Philadelphia Chromosome Positive Chronic Myeloid Leukemia". U.S. Food and Drug ... which has the Philadelphia chromosome. It may be used both in initial cases of chronic phase CML as well as in accelerated and ...
The main targets of dasatinib are BCR/Abl (the "Philadelphia chromosome"), Src, c-Kit, ephrin receptors, and several other ... and adults with newly diagnosed Philadelphia-chromosome-positive (Ph+) chronic myelogenous leukaemia (CML) in the chronic phase ... In the EU dasatinib is indicated for children with newly diagnosed Philadelphia chromosome-positive chronic myelogenous ... Specifically it is used to treat cases that are Philadelphia chromosome-positive (Ph+). It is taken by mouth. Common adverse ...
Philadelphia Chromosome is an example of this type of translocation event. This chromosome was discovered in 1960 by Peter ... and it is a fusion of parts of DNA from chromosome 22 and chromosome 9. The broken end of chromosome 22 contains the "BCR" gene ... Another example of an oncogene is the Bcr-Abl gene found on the Philadelphia chromosome, a piece of genetic material seen in ... Src-family, Syk-ZAP-70 family, and BTK family of tyrosine kinases, the Abl gene in CML - Philadelphia chromosome. colorectal ...
This gene is a partner in a fusion gene with the BCR gene in the Philadelphia chromosome, a characteristic abnormality in ... "Interaction of BCR-ABL with the retinoblastoma protein in Philadelphia chromosome-positive cell lines". Int. J. Hematol. 65 (2 ... located on chromosome 9. c-Abl is sometimes used to refer to the version of the gene found within the mammalian genome, while v ... gene on chromosome 22. This new fusion gene, BCR-ABL, encodes an unregulated, cytoplasm-targeted tyrosine kinase that allows ...
Most importantly, the Philadelphia chromosome and other BCR/ABL fusion genes are not detected. Peripheral blood neutrophilia ... and the absence of the Philadelphia chromosome or a BCR/ABL fusion gene. The most common clinical finding is hepatosplenomegaly ...
"Interaction of BCR-ABL with the retinoblastoma protein in Philadelphia chromosome-positive cell lines". International Journal ... In humans, the protein is encoded by the RB1 gene located on chromosome 13-more specifically, 13q14.1-q14.2. If both alleles of ... chromosome condensation, and heterochromatin formation. Rb has also been implicated in regulating metabolism through ...
1984). "Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome 22". Cell. 36 (1): 93-9 ... 1995). "Sequence and analysis of the human ABL gene, the BCR gene, and regions involved in the Philadelphia chromosomal ...
1984). "Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome 22". Cell. 36 (1): 93-9 ... 1990). "A novel variant of the bcr-abl fusion product in Philadelphia chromosome-positive acute lymphoblastic leukemia". ... 1995). "Sequence and analysis of the human ABL gene, the BCR gene, and regions involved in the Philadelphia chromosomal ... BCR in some patients with Philadelphia-positive leukemia". Blood. 78 (4): 1078-84. doi:10.1182/blood.V78.4.1078.1078. PMID ...
Philadelphia chromosome t(9 ABL; 22 BCR). *Acute myeloblastic leukemia with maturation t(8 RUNX1T1;21 RUNX1) ... the long arm of chromosome 21 is attached to another chromosome, often chromosome 14.[69] In a male affected with Down syndrome ... When combined with a normal cell from the other parent, the baby has 47 chromosomes, with three copies of chromosome 21.[2][62] ... or ring chromosome. These contain additional material from chromosome 21 and occur in about 2.5% of cases.[20][61] An ...
Approval was also granted for T315I-positive and T315I-positive Philadelphia chromosome positive acute lymphoblastic leukemia. ... and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). It is a multi-targeted tyrosine-kinase inhibitor ... or blast phase chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia for whom no other ... Ph+ ALL is a subtype of acute lymphoblastic leukemia that carries the Ph+ chromosome that produces BCR-ABL. It has a more ...
The Philadelphia chromosome or Philadelphia translocation (Ph) is a specific genetic abnormality in chromosome 22 of leukemia ... The Philadelphia chromosome is designated Ph (or Ph) chromosome and designates the shortened chromosome 22 which encodes the ... termed a derivative chromosome, or der 9), and a truncated chromosome 22 (the Philadelphia chromosome, 22q-).[5][6] In ... The chromosomal defect in the Philadelphia chromosome is a reciprocal translocation, in which parts of two chromosomes, 9 and ...
Philadelphia chromosome (en); كروموسوم فيلادلفيا (ar); Philadelphský chromozom (cs); Philadelphia chromosome or Philadelphia ... Cromosoma Philadelphia Philadelphia chromosome or Philadelphia translocation is a specific chromosomal abnormality that is ... Philadelphia chromosome or Philadelphia translocation is a specific chromosomal abnormality that is associated with chronic ... Philadelphia chromosome or Philadelphia translocation is a specific chromosomal abnormality that is associated with chronic ...
The outcomes and prognosis of adolescents and young adults with Philadelphia chromosome-negative ALL differs from that of ... Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia in Adolescent and Young Adults The following represents ... The management of Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) has changed dramatically in recent ... Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia in Adolescents and Young Adults. ...
... www.mayoclinic.org/diseases-conditions/chronic-myelogenous-leukemia/multimedia/how-the-philadelphia-chromosome-forms/img- ...
Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias.. Talpaz M1, Shah NP, Kantarjian H, Donato N, Nicoll ... The BCR-ABL tyrosine kinase inhibitor imatinib is effective in Philadelphia chromosome-positive (Ph-positive) leukemias, but ...
Book Trailer for The Philadelphia Chromosome Posted February 18, 2013 by Jessica Wapner in Books, The Philadelphia Chromosome ... Readers of this blog have been hearing about my first book, "The Philadelphia Chromosome," out this May. Well, the book now has ...
Bone marrow cells that contain the Philadelphia chromosome are often found in chronic myelogenous leukemia and sometimes found ... An abnormality of chromosome 22 in which part of chromosome 9 is transferred to it. ... Philadelphia chromosome listen (FIH-luh-DEL-fee-uh KROH-muh-some) An abnormality of chromosome 22 in which part of chromosome 9 ... Philadelphia chromosome. A piece of chromosome 9 and a piece of chromosome 22 break off and trade places. The BCR-ABL gene is ...
Beyond the Philadelphia Chromosome. Speaker: Dr. Arline Cohn. This years talk will describe the discovery of the Philadelphia ... Lyceum Society: Beyond the Philadelphia Chromosome. Monday, May 5, 2014. The New York Academy of Sciences ... Chromosome, the development of a treatment for the disease that it caused, (chronic myeloid leukemia), how that led to a better ...
Coloured light micrograph of a female karyotype (chromosome set) with one defective chromosome each from pairs 9 and 22. ... Philadelphia chromosome. Coloured light micrograph of a female karyotype (chromosome set) with one defective chromosome each ... made defective chromosome 9 larger and shrunk defective chromosome 22. In a bone marrow stem cell, the chromosome 22 defect ... The defects, on the right-hand chromosomes of the two pairs, cause chronic myelogenous leukaemia (CML). The 46 chromosomes of a ...
... philadelphia+chromosome+positive+chronic+myelocytic+leukemia? Find a list of current medications, their possible side effects, ... dosage, and efficacy when used to treat or reduce the symptoms of chronic+phase+philadelphia+chromosome+positive+chronic+ ... Considering taking medication to treat chronic+phase+philadelphia+chromosome+positive+chronic+myelocytic+leukemia? Below is a ... 10 medications found for chronic+phase+philadelphia+chromosome+positive+chronic+myelocytic+leukemia ...
... for treating Philadelphia-chromosome-negative precursor B-cell acute lymphoblastic leukaemia in adults ... This means that, if a patient has Philadelphia-chromosome-negative relapsed or refractory precursor B-cell acute lymphoblastic ... Blinatumomab for previously treated Philadelphia-chromosome-negative acute lymphoblastic leukaemia. Technology appraisal ...
"Philadelphia Chromosome" by people in Harvard Catalyst Profiles by year, and whether "Philadelphia Chromosome" was a major or ... "Philadelphia Chromosome" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical ... How we approach Philadelphia chromosome-positive acute lymphoblastic leukemia in children and young adults. Pediatr Blood ... The landscape of BCR-ABL mutations in patients with Philadelphia chromosome-positive leukaemias in the era of second-generation ...
An aberrant form of human CHROMOSOME 22 characterized by translocation of the distal end of chromosome 9 from 9q34, to the long ... arm of chromosome 22 at 22q11. It is present in the bone marrow cells of 80 to 90 per cent of patients with chronic myelocytic ... Ph 1 Chromosome; 1 Chromosome, Ph; 1 Chromosomes, Ph; Chromosome, Ph 1; Chromosome, Ph1; Chromosome, Philadelphia; Chromosomes ... Chromosomes*Mammalian Chromosomes*Human Chromosomes*21-22 and Y Human Chromosomes*Pair 22 Human Chromosomes*Philadelphia ...
Study Evaluating SKI-606 (Bosutinib) In Philadelphia Chromosome Positive Leukemias. The safety and scientific validity of this ... Philadelphia Chromosome. Neoplasms by Histologic Type. Neoplasms. Myeloproliferative Disorders. Bone Marrow Diseases. ... Long-term patient-reported outcomes from an open-label safety and efficacy study of bosutinib in Philadelphia chromosome- ... bcr-Abl is a protein resulting from the transcription of the Philadelphia chromosome following 9:22 chromosomal translocation, ...
The presence of Philadelphia chromosome does not confer poor prognosis in adult pre-B acute lymphoblastic leukaemia in the ... Ponatinib in refractory Philadelphia chromosome-positive leukemias. N Engl J Med. 2012 Nov 29. 367(22):2075-88. [Medline]. ... Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood. 2004 Jun ... What is the role of dasatinib in the treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL)?. ...
The (9;22) translocation which produces the Philadelphia (Ph1) chromosome activates the abl oncogene from chromosome 9 by ... Molecular Heterogeneity of Adult Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia. K. Schaefer-Rego, Z. Arlin, L. ... Molecular Heterogeneity of Adult Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia. K. Schaefer-Rego, Z. Arlin, L. ... Molecular Heterogeneity of Adult Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia. K. Schaefer-Rego, Z. Arlin, L. ...
Molecular pathology of tumor-initiating cells: Lessons from Philadelphia chromosome-positive leukemia. Authors. *. Kazuhito ... chromosome-positive leukemia. The abnormal Ph chromosome, which arises from a translocation creating the BCR-ABL1 fusion gene, ... In this review, we examine recent advances in cancer stem cell research that have been generated from studies of Philadelphia ( ...
We present the results of treatment of Philadelphia chromosome-negative (Ph-) ALL patients over 55 yr treated in the PETHEMA ... Results of the PETHEMA ALL-96 trial in elderly patients with Philadelphia chromosome-negative acute lymphoblastic leukemia.. ...
Post-Frontline Sequential Treatment of Adult Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia. The safety and ... Philadelphia Chromosome. Neoplasms by Histologic Type. Neoplasms. Lymphoproliferative Disorders. Lymphatic Diseases. ... Ancillary Observational Study of Post-Frontline Sequential Treatment of Adult Philadelphia Chromosome-Positive (Ph+) Acute ... Chromosome Aberrations. Pathologic Processes. Dasatinib. Blinatumomab. Antibodies, Bispecific. Immunologic Factors. ...
... Prajwal Boddu,1 C ... The initial plan of treatment was to treat along the lines of Philadelphia negative B-ALL/LBL. During this time, fluorescence ...
The Philadelphia chromosome results from a translocation of genetic material between chromosomes 9 and 22. Read the full ... Philadelphia chromosome positive (Ph+) describes a leukemia that carries a specific chromosomal translocation. ... Philadelphia Chromosome Positive. Philadelphia chromosome positive (Ph+) describes a leukemia that carries a specific ... The Philadelphia chromosome results from a translocation of genetic material between chromosomes 9 and 22. From this new ...
... to the long arm of chromosome 22 at 22q11. It is present in the bone marrow cells of 80 to 90 per cent of patients with chronic ... An aberrant form of human CHROMOSOME 22 characterized by translocation of the distal end of chromosome 9 from 9q34, ... Philadelphia Chromosome. Known as: Chromosome, Philadelphia, Ph 1 Chromosomes, Philadelphia Chromosome [Disease/Finding] (More) ... Ponatinib in refractory Philadelphia chromosome-positive leukemias.. *Jorge E Cortes, Hagop M. Kantarjian, +13 authors Moshe ...
The Philadelphia chromosome has been identified in most cases of a slowly progressing form of blood cancer called chronic ... The presence of the Philadelphia chromosome can help predict how a cancer will progress and provides a target for molecular ... It fuses part of a specific gene from chromosome 22 (the BCR gene) with part of another gene from chromosome 9 (the ABL gene). ... of genetic material between chromosomes 9 and 22 is associated with several types of blood cancer known as leukemias. This ...
Here, we report a case of a pregnant woman with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL) who ...
Jack was just 9 days old when his family learned he also had chromosome 22q11.2 deletion, a rare chromosomal difference. ... Chromosome 22q11.2 deletion. Jack was nine days old when the Genetics team came to speak with us about chromosome 22q11.2 ... We thank God for our proximity to Philadelphia, because the hospital has been a great comfort to us. ... In fact, the leading research on chromosome 22q11.2 deletion is conducted there. Genetic disorders are gaining public ...
Phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. N Engl J Med. 2013;369(19):1783-96.CrossRefGoogle ... Ponatinib efficacy and safety in Philadelphia chromosome-positive leukemia: final 5-year results of the phase 2 PACE trial. ... Ponatinib in Japanese patients with Philadelphia chromosome-positive leukemia, a phase 1/2 study. Int J Hematol. 2017;106(3): ... Combination of hyper-CVAD with ponatinib as first-line therapy for patients with Philadelphia chromosome-positive acute ...
BMSs Sprycel Tablets Now Approved in Combination with Chemotherapy in Certain Pediatric Patients with Philadelphia Chromosome- ... Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy ... Certain Pediatric Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia * Sprycel is the first and only ... Newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase ...
An explanation of the Philadelphia chromosome including where it comes from, how it effects the bone marrow, and disease that ... What Is the Philadelphia Chromosome? The Philadelphia chromosome has a story and a setting, but for practical purposes, it can ... How the Philadelphia Chromosome Identifies Cancer The Philadelphia chromosome is a specific genetic change that has become a ... "Philadelphia-chromosome-positive (Ph+) chronic myeloid leukemia" (CML) or "Philadelphia chromosome-positive (Ph+) acute ...
Philadelphia Chromosome Positive Recruiting Phase 3 Trials for Tioguanine (DB00352). Back to Philadelphia Chromosome Positive ... Imatinib Mesylate and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute ...
  • PRINCETON, N.J.--( BUSINESS WIRE )-- Bristol-Myers Squibb Company (NYSE:BMY) today announced the U.S. Food and Drug Administration (FDA) has expanded the indication for Sprycel ® (dasatinib) tablets to include the treatment of pediatric patients one year of age and older with newly diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) in combination with chemotherapy. (businesswire.com)
  • More recently, Tasigna (nilotinib) was approved to treat adults who have newly diagnosed Philadelphia chromosome-positive (Ph+) CML in chronic phase. (verywellhealth.com)
  • This randomized phase III trial studies how well imatinib mesylate and combination chemotherapy work in treating patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia. (rochester.edu)
  • Earlier in 2018 , nilotinib (Tasigna) was approved for the treatment of pediatric patients aged ≥ 1 year with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (CML-CP) or Philadelphia chromosome-positive CML-CP resistant or intolerant to prior tyrosine kinase inhibitor therapy. (ascopost.com)
  • n = 11) and CAMN107A2203 in pediatric patients with Philadelphia chromosome-positive CML-CP resistant or intolerant to imatinib or dasatinib (n = 33) and newly diagnosed Philadelphia chromosome-positive CML-CP (n = 25). (ascopost.com)
  • In 25 patients with newly diagnosed Philadelphia chromosome-positive CML-CP, the major molecular response was achieved in 15 patients (60.0%) at 12 cycles. (ascopost.com)
  • Carmichael's Community Book Club will start 2015 with reading The Philadelphia Chromosome by Jessica Wapner. (carmichaelsbookstore.com)
  • Science journalist Jessica Wapner brings this story vividly to life in her book, The Philadelphia Chromosome. (foxchase.org)
  • In [ The Philadelphia Chromosome ], Jessica Wapner chronicles the ensuing decades of laborious scientific inquiry and industrial ingenuity that led to the discovery of Gleevec, the first drug designed to attack cancer at the genetic level. (townecenterbooks.com)
  • A piece of chromosome 9 and a piece of chromosome 22 break off and trade places. (cancer.gov)
  • for some reason unbeknownst to all, a small piece of chromosome 22 breaks off and saunters its' way over to chromosome 9. (leukemiasurvivor.co)
  • These changes include an extra piece of chromosome 22 in each cell (partial trisomy), a missing segment of the chromosome in each cell (partial monosomy), and a circular structure called ring chromosome 22 that is caused by the breakage and reattachment of both ends of the chromosome. (wikipedia.org)
  • When all the genetic material in the cell of a human being gets packaged up, there are 23 pairs of chromosomes, for a total of 46 chromosomes in each cell. (verywellhealth.com)
  • A fruit fly, for example, has four pairs of chromosomes, while a rice plant has 12 and a dog, 39. (verywellhealth.com)
  • Chromosome 22 is one of the 23 pairs of chromosomes in human cells. (wikipedia.org)
  • The defects, on the right-hand chromosomes of the two pairs, cause chronic myelogenous leukaemia (CML). (sciencephoto.com)
  • Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. (nih.gov)
  • The BCR-ABL tyrosine kinase inhibitor imatinib is effective in Philadelphia chromosome-positive (Ph-positive) leukemias, but relapse occurs, mainly as a result of the outgrowth of leukemic subclones with imatinib-resistant BCR-ABL mutations. (nih.gov)
  • This is an open-label, continuous daily dosing, two-part safety and efficacy study of SKI-606 ( bosutinib ) in Philadelphia chromosome positive leukemias (Ph+). (clinicaltrials.gov)
  • A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. (semanticscholar.org)
  • Ponatinib in refractory Philadelphia chromosome-positive leukemias. (semanticscholar.org)
  • The Philadelphia chromosome is a rearrangement (translocation) of genetic material between chromosomes 9 and 22 is associated with several types of blood cancer known as leukemias. (genome.gov)
  • Sherbenou D, Druker B. Applying the discovery of the Philadelphia chromosome . (verywellhealth.com)
  • 2020 marks the 60th anniversary of the publications by Peter C. Nowell and David A. Hungerford that announced the discovery of the Philadelphia Chromosome. (foxchase.org)
  • The discovery of the Philadelphia Chromosome took place in 1959 under a Fox Chase Cancer Center microscope and was the result of a collaboration between two scientists from both Fox Chase (then known as the Institute for Cancer Research) and the University of Pennsylvania. (foxchase.org)
  • The discovery of the Philadelphia chromosome as a hallmark of chronic myelogenous leukemia in 1960 by Peter Nowell provided evidence for a genetic link to cancer. (semanticscholar.org)
  • Cancer is one of them, after the discovery of the Philadelphia chromosome, the role of chromosome alterations in oncogenic activation is cleared. (geneticeducation.co.in)
  • Before the discovery of the Philadelphia chromosome, scientists didn't know that DNA alterations could cause cancer. (cancer.gov)
  • The discovery of the Philadelphia chromosome and BCR-ABL, supported in part by NCI, demonstrated for the first time that a genetic alteration could cause cancer. (cancer.gov)
  • This chromosome is defective and unusually short because of reciprocal translocation , t(9;22)(q34;q11), of genetic material between chromosome 9 and chromosome 22 , and contains a fusion gene called BCR-ABL1 . (wikipedia.org)
  • The chromosomal defect in the Philadelphia chromosome is a reciprocal translocation , in which parts of two chromosomes, 9 and 22, swap places. (wikipedia.org)
  • The Philadelphia chromosome (Ph) resulting from the reciprocal translocation of chromosomes 9 and 22 [t(9:22)(q34;q11)] gave rise to a fusion BCR-ABL gene. (uhhospitals.org)
  • The reciprocal translocation between chromosome 9 and 22 results in the fusion of two genes viz BCR and ABL1. (geneticeducation.co.in)
  • The presence of the Philadelphia chromosome can help predict how a cancer will progress and provides a target for molecular therapies. (genome.gov)
  • As part of their assessment, doctors will look for the presence of the Philadelphia chromosome to help determine if a patient is affected by particular types of leukemia. (verywellhealth.com)
  • Chronic myelogenous leukemia (CML) is a pluripotent stem cell disease characterized by the presence of the Philadelphia chromosome and the bcr-abl gene. (dovepress.com)
  • The Ph chromosome is a translocation, or rearrangement, of chromosomes 9 and 22. (cancer.ca)
  • Further, the unusual rearrangement of chromosome caused by balanced translocation or unbalanced translocation. (geneticeducation.co.in)
  • Philadelphia chromosome‐negative chronic myelogenous leukemia with rearrangement of the breakpoint cluster region. (elsevier.com)
  • What is the role of dasatinib in the treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL)? (medscape.com)
  • Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. (semanticscholar.org)
  • Adding medications such as imatinib and dasatinib that specifically inhibit the BCR-ABL1 tyrosine kinase (tyrosine kinase inhibitors or TKIs) to chemotherapy led to dramatic improvements in cure rates for children with Philadelphia chromosome positive ALL. (chop.edu)
  • PRINCETON, N.J.--(BUSINESS WIRE) November 10, 2017 --Bristol-Myers Squibb Company (NYSE:BMY) today announced the U.S. Food and Drug Administration (FDA) has expanded the indication for Sprycel ( dasatinib ) tablets to include the treatment of children with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia ( CML ) in chronic phase (CP). (drugs.com)
  • The FDA's decision to approve the expanded use of Sprycel in children with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase may bring new hope to these patients and their families. (drugs.com)
  • Dasatinib is an important new option to help address the unmet needs of children with Philadelphia chromosome-positive CML in chronic phase. (drugs.com)
  • OBJECTIVE To determine whether dasatinib given at 80 mg/m 2 is more effective than imatinib at 300 mg/m 2 to improve event-free survival of children with Philadelphia chromosome-positive ALL, in the context of intensive chemotherapy without prophylactic cranial irradiation. (confex.com)
  • The Philadelphia chromosome results from a translocation of genetic material between chromosomes 9 and 22. (primeoncology.org)
  • The Philadelphia chromosome often abbreviated as "Ph chromosome" is originated due to the exchange of genetic material between two chromosome during recombination. (geneticeducation.co.in)
  • Because of the exchange of genetic material between chromosome 9 and 22, some gene sequences from chromosome 9 migrates on chromosome 22 and vice verse, noticed usually in the chronic myeloid leukemia. (geneticeducation.co.in)
  • The present translocation is reciprocal (exchange of genetic material between two non-homologous chromosomes) and cytologically written as t(9;22)(q32;q11). (geneticeducation.co.in)
  • During the translocation of genetic material, the ABL1 gene segment translocates to the q arm of the chromosome 22 near the BCR gene which results in the fusion of the BCR-ABL1 gene. (geneticeducation.co.in)
  • A small extra chromosome is made up of genetic material from chromosome 22 that has been abnormally duplicated (copied). (wikipedia.org)
  • A crucial link between genetics and cancer emerged in a US lab in 1959, as researcher David Hungerford peered down a microscope at an abnormally small chromosome. (townecenterbooks.com)
  • Curious to know if the small chromosome was a common feature in CML, they eagerly examined leukemia cells from more people with CML. (cancer.gov)
  • Efficacy of Ponatinib Versus Earlier Generation Tyrosine Kinase Inhibitors for Front-line Treatment of Newly Diagnosed Philadelphia-positive Acute Lymphoblastic Leukemia. (harvard.edu)
  • Prognostic significance of additional cytogenetic abnormalities in newly diagnosed patients with Philadelphia chromosome-positive chronic myelogenous leukemia treated with interferon-alpha: a Cancer and Leukemia Group B study. (biomedsearch.com)
  • On December 19, 2017, bosutinib (Bosulif) was granted accelerated approval for the treatment of newly diagnosed chronic-phase Philadelphia chromosome-positive chronic myeloid leukemia (CML). (ascopost.com)
  • THE RECOMMENDED DOSE of bosutinib in newly diagnosed chronic-phase Philadelphia chromosome-positive CML is 400 mg once daily with food until disease progression or intolerance. (ascopost.com)
  • The Philapdelphia chromosome negative chronic myeloproliferative neoplasia (MPN) encompass the diseases essential thrombocytemia, polycythemia vera and myelofibrosis, which are incurable neoplasms of the hematopoietic cells in the bone marrow. (herlevhospital.dk)
  • This means that, if a patient has Philadelphia-chromosome-negative relapsed or refractory precursor B-cell acute lymphoblastic leukaemia and the doctor responsible for their care thinks that blinatumomab is the right treatment, it should be available for use, in line with NICE's recommendations. (nice.org.uk)
  • Combination of hyper-CVAD with ponatinib as first-line therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia: a single-centre, phase 2 study. (springer.com)
  • BCR-ABL, a constitutively activated tyrosine kinase, is the oncogene that causes Philadelphia-chromosome-positive (Ph+) leukaemia. (nih.gov)
  • Intrahepatikus cholostasis tüneteivel kezdödö Philadelphia chromosoma negatív chronikus myeloid leukaemia. (elsevier.com)
  • Due to the translocation between chromosome 9 and 22, BCR-ABL1 gene formation occurred at chromosome 22 consequence in activation of oncogene which leads to the acute myeloid leukaemia, called the Philadelphia chromosome or Ph chromosome. (geneticeducation.co.in)
  • The Ph chromosome is also reported in some cases of Acute Lymphoblastic Leukemia (25-30%) and mixed-phenotype acute leukaemia. (geneticeducation.co.in)
  • Hyper-CVAD plus ponatinib versus hyper-CVAD plus dasatinib as frontline therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: a propensity score analysis. (springer.com)
  • Research led by Center for Childhood Cancer Research director Stephen P. Hunger, MD and his collaborators determined that one major subtype of Ph-like ALL had abnormalities in the Abl protein itself or in closely related proteins and showed that, as with Philadelphia chromosome-positive ALL, these abnormalities were very responsive to imatinib or dasatinib. (chop.edu)
  • The patient was diagnosed with Philadelphia chromosome-positive B-lymphoblastic lymphoma (B-LBL), treated with hyper-cyclophosphamide, vincristine, doxorubicin plus dasatinib and achieved complete remission. (bloodjournal.org)
  • Determine the toxicities of dasatinib in pediatric patients with imatinib mesylate-resistant Philadelphia chromosome-positive (Ph+) leukemia. (knowcancer.com)
  • In this ongoing Phase 1/2 study (NCT01667133), we evaluated ponatinib and assessed its recommended dose in Japanese patients with chronic myeloid leukemia (CML) resistant/intolerant to dasatinib or nilotinib, or with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) resistant/intolerant to ≥1 tyrosine kinase inhibitor (TKI). (elsevier.com)
  • An aberrant form of human CHROMOSOME 22 characterized by translocation of the distal end of chromosome 9 from 9q34, to the long arm of chromosome 22 at 22q11. (harvard.edu)
  • The following are some of the gene count estimates of human chromosome 22. (wikipedia.org)
  • The following is a partial list of genes on human chromosome 22. (wikipedia.org)
  • The landscape of BCR-ABL mutations in patients with Philadelphia chromosome-positive leukaemias in the era of second-generation tyrosine kinase inhibitors. (harvard.edu)
  • In contrast to these findings in chronic myelogenous leukemia, a small number of patients with Ph 1 (+) acute lymphoblastic leukemia (ALL) have been studied and were found to lack the bcr/abl fusion gene [bcr(-)], but to have a new activation of abl , by recombination with an as yet undetermined region on chromosome 22. (aacrjournals.org)
  • Results of the PETHEMA ALL-96 trial in elderly patients with Philadelphia chromosome-negative acute lymphoblastic leukemia. (nih.gov)
  • We present the results of treatment of Philadelphia chromosome-negative (Ph-) ALL patients over 55 yr treated in the PETHEMA ALL-96 trial. (nih.gov)
  • Ponatinib in Japanese patients with Philadelphia chromosome-positive leukemia, a phase 1/2 study. (springer.com)
  • Does post-transplant maintenance therapy with tyrosine kinase inhibitors improve outcomes of patients with high-risk philadelphia chromosome-positive leukemia? (springer.com)
  • As treatments have advanced in recent years, we've seen improvements in outcomes for pediatric patients with Ph+ ALL overall, but there remains a need for additional options," 3 said Stephen Hunger, MD, lead study author, chief of the division of oncology and director of the Center for Childhood Cancer Research at Children's Hospital of Philadelphia. (businesswire.com)
  • Patients with ALL who possess this chromosome are at a higher risk for poor outcomes than children who have ALL without this chromosome. (chop.edu)
  • The abnormalities present in leukemia cells of patients with Ph-like ALL are highly similar to those of patients with Philadelphia chromosome positive ALL, but these cases do not contain BCR-ABL1 fusion. (chop.edu)
  • Giving imatinib mesylate and combination chemotherapy may work better in treating patients with Philadelphia chromosome positive acute lymphoblastic leukemia. (rochester.edu)
  • In December, the FDA granted accelerated approval to ponatinib (Iclusig) for the treatment of adult patients with chronic-, accelerated-, or blast-phase chronic myeloid leukemia (CML) that is resistant or intolerant to prior tyrosine kinase inhibitor therapy or Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) that is resistant or intolerant to prior tyrosine kinase inhibitor therapy. (ascopost.com)
  • In accelerated- and blast-phase CML and Philadelphia chromosome-positive ALL, ponatinib's effectiveness was determined by the number of patients who experienced major hematologic response. (ascopost.com)
  • 41% of patients with Philadelphia chromosome-positive ALL achieved major hematologic response for a median duration of 3.2 months. (ascopost.com)
  • Pfizer announced that the FDA has approved Bosulif (bosutinib) for the treatment of adult patients with chronic, accelerated, or blast phase Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) with resistance, or intolerance to prior therapy. (empr.com)
  • Secondary cytogenetic abnormalities at diagnosis of Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) have been associated with an inferior outcome in reported series of largely chemotherapy-treated patients. (biomedsearch.com)
  • In 44 patients with resistant or intolerant Philadelphia chromosome-positive CML-CP, major molecular response (BCR-ABL/ABL ≤ 0.1% international scale) was achieved in 18 patients (40.9%) at 12 cycles. (ascopost.com)
  • In vitro, nilotinib inhibited BCR-ABL-mediated proliferation of murine leukemic cell lines and human cell lines derived from patients with Philadelphia chromosome-positive CML. (ascopost.com)
  • In studies conducted in adult Philadelphia chromosome-positive CML patients, dose escalation by increments of 100 mg once daily to a maximum of 600 mg once daily was permitted in patients who did not achieve or maintain a hematologic, cytogenetic, or molecular response and who did not have grade ≥ 3 adverse events at the recommended starting dosage. (ascopost.com)
  • Patients with Philadelphia chromosome-like B-cell lymphoblastic leukemia (Ph-like or BCR-ABL1 -like BALL) experience high relapse rates and are difficult to cure with conventional chemotherapy. (haematologica.org)
  • Allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission is a standard of care for adult patients with Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) and high risk of relapse. (eur.nl)
  • AMGN ) today announced that the European Commission (EC) has approved an expanded indication for BLINCYTO ® (blinatumomab) monotherapy to include adult patients with Philadelphia chromosome negative (Ph-) CD19 positive B-cell precursor acute lymphoblastic leukemia (ALL) in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1 percent. (pharmalive.com)
  • During his doctoral research work on the chromosome, he found this unusual chromosomal imbalance in the positive leukemia patients, first time. (geneticeducation.co.in)
  • In 1960, Drs. Nowell and Hungerford examined cancer cells from two patients with CML and noticed something peculiar-one of the 46 chromosomes was abnormally short. (cancer.gov)
  • Sure enough, they found seven more patients who had the same abnormal chromosome. (cancer.gov)
  • Further research showed that 95% of patients with CML have the Philadelphia chromosome. (cancer.gov)
  • BACKGROUND:Resistance to tyrosine kinase inhibitors in patients with chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) is frequently caused by mutations in the BCR-ABL kinase domain. (elsevier.com)
  • Five to 10% of patients with chronic myelogenous leukemia (CML) do not have the Philadelphia chromosome (Ph), but one‐third of them have rearrangements of the breakpoint cluster region (BCR‐positive). (elsevier.com)
  • Tyrosine kinase inhibitors (TKIs) were currently used as front line chemotherapy agents in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) patients. (biomedcentral.com)
  • METHODS: This study assessed the impact of baseline cytogenetics on the outcomes of 428 adult patients with Philadelphia chromosome-negative ALL who were receiving frontline chemotherapy. (elsevier.com)
  • Chromosome changes, or abnormalities, are a prognostic factor for CML. (cancer.ca)
  • 22q11.2 distal deletion syndrome 22q13 deletion syndrome Other chromosomal conditions: Other changes in the number or structure of chromosome 22 can have a variety of effects, including mental retardation, delayed development, physical abnormalities, and other medical problems. (wikipedia.org)
  • If there are other chromosome changes or several chromosome changes, the CML usually has a shorter chronic phase and a less favourable prognosis. (cancer.ca)
  • In the past, having leukemia cells with the Ph chromosome (referred to as Ph-positive ALL, or Ph+ ALL) used to mean a less favourable prognosis. (cancer.ca)
  • range 16-69) with Philadelphia chromosome (Ph+) positive in chronic phase CML with oral imatinib mesylate at daily doses of 400 mg. (curehunter.com)
  • The management of Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) has changed dramatically in recent years. (medscape.com)
  • Considering taking medication to treat chronic+phase+philadelphia+chromosome+positive+chronic+myelocytic+leukemia? (webmd.com)
  • Below is a list of common medications used to treat or reduce the symptoms of chronic+phase+philadelphia+chromosome+positive+chronic+myelocytic+leukemia. (webmd.com)
  • Ponatinib efficacy and safety in Philadelphia chromosome-positive leukemia: final 5-year results of the phase 2 PACE trial. (harvard.edu)
  • The Philadelphia chromosome or Philadelphia translocation ( Ph ) is a specific genetic abnormality in chromosome 22 of leukemia cancer cells (particularly chronic myeloid leukemia (CML) cells). (wikipedia.org)
  • Bone marrow cells that contain the Philadelphia chromosome are often found in chronic myelogenous leukemia and sometimes found in acute lymphocytic leukemia. (cancer.gov)
  • Phosphatidylinositol-3 kinase activity is regulated by BCR/ABL and is required for the growth of Philadelphia chromosome-positive cells. (semanticscholar.org)
  • The Philadelphia chromosome is a specific finding in the genes of a person's white blood cells-a finding that has implications for leukemia. (verywellhealth.com)
  • The Philadelphia chromosome is only found in the affected blood cells. (verywellhealth.com)
  • Cytogenetic Response (CyR) is based on the prevalence of Philadelphia chromosome positive (Ph+) metaphases among cells in metaphase on a bone marrow (BM) aspirate. (clinicaltrials.gov)
  • The cells show L3 morphology (Burkitt-like lymphoma) with coexpression of TdT and surface light chains in addition to an MYC gene translocation and Philadelphia chromosome. (hindawi.com)
  • The drug's effectiveness was demonstrated by a reduction in the percentage of cells expressing the Philadelphia chromosome genetic mutation to less than 35%, a major cytogenetic response. (ascopost.com)
  • Introduction: The BCR-ABL1 tyrosine kinase induces malignant transformation of B cells at the pre-B cell checkpoint and induces Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). (aacrjournals.org)
  • This 40 years of research, starting from the discovery of an abnormal chromosome in CML cells and ending in the design of a drug that can negate the consequences of that chromosomal change, illustrate how slow yet steady progress in cancer research is having a positive impact on the outlook for people with cancer. (foxchase.org)
  • Chromosomes are structures in the cells that contain genes. (leukemiasurvivor.co)
  • Philadelphia chromosome - Phil·a·del·phia chromosome .fil ə del fē ə n an abnormally short chromosome 22 that is found in the hematopoietic cells of persons affected with chronic myelogenous leukemia and lacks the major part of its long arm which has usu. (enacademic.com)
  • About 95% of adults with CML have leukemia cells with the Ph chromosome. (cancer.ca)
  • This means a decrease to 35% or less of the leukemia cells with the Ph chromosome. (cancer.ca)
  • The most common abnormality in the leukemia cells of people with ALL is the Philadelphia (Ph) chromosome. (cancer.ca)
  • When Chromosome 9 and 22 switch at this place, BCR becomes fused to the gene ABL, making cells divide uncontrollably. (genomeyear.net)
  • Despite the popular belief that cancer was not caused by genetic changes, Dr. Nowell was interested in the chromosomes (structures that carry genetic information) of leukemia cells. (cancer.gov)
  • A monoclonal antibody which primarily reacted with Philadelphia chromosome (Ph 1 )-positive ALL cells was produced. (elsevier.com)
  • abstract = "A monoclonal antibody which primarily reacted with Philadelphia chromosome (Ph1)-positive ALL cells was produced. (elsevier.com)
  • Chromosome 22 is the second smallest human chromosome, spanning about 49 million DNA base pairs and representing between 1.5 and 2% of the total DNA in cells. (wikipedia.org)
  • This chromosomal abnormality, which is commonly called the Philadelphia chromosome, is found only in cancer cells. (wikipedia.org)
  • BCR-ABL1 compound mutations combining key kinase domain positions confer clinical resistance to ponatinib in Ph chromosome-positive leukemia. (springer.com)
  • Though the Philadelphia chromosome is often thought of in connection with CML and ALL, it can also come up in other contexts, such as "variant Philadelphia translocations," and "Philadelphia chromosome-negative chronic myeloproliferative disease. (verywellhealth.com)
  • In a bone marrow stem cell, the chromosome 22 defect causes the CML increased white blood cell count. (sciencephoto.com)
  • [2] (Some cases are confounded by either a cryptic translocation that is invisible on G-banded chromosome preparations, or a variant translocation involving another chromosome or chromosomes as well as the long arm of chromosomes 9 and 22. (wikipedia.org)
  • The chromosomal translocation is a type of genetic mutation in which one part or the portion or an entire arm of a chromosome deleted from one chromosome and attached to another chromosome. (geneticeducation.co.in)
  • The legacy of the Philadelphia chromosome. (semanticscholar.org)
  • The legacy of the Philadelphia chromosome now serves as a paradigm for how basic science discoveries can lead to effective new approaches for the treatment of human disease. (semanticscholar.org)
  • On December 3, 2014, blinatumomab (Blincyto) was granted accelerated approval for use in treating Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). (ascopost.com)
  • This review illustrates the entity of Philadelphia chromosome-like ALL, encountered driver mutations, and potential targeted treatment with tyrosine-kinase inhibitors. (bestbits.ca)
  • The post Planning Your Next Move in Philadelphia Chromosome Positive Leukaemias appeared first on European Medical Journal . (digitalistechnology.co.uk)
  • Philadelphia chromosome positive (Ph+) describes a leukemia that carries a specific chromosomal translocation. (primeoncology.org)
  • The Philadelphia chromosome (Ph) is a shortened chromosome 22 generated by a balanced t(9;22) chromosomal translocation. (bloodjournal.org)
  • This gene is the ABL1 gene of chromosome 9 juxtaposed onto the breakpoint cluster region BCR gene of chromosome 22, coding for a hybrid protein: a tyrosine kinase signalling protein that is "always on", causing the cell to divide uncontrollably by interrupting the stability of the genome and impairing various signaling pathways governing the cell cycle. (wikipedia.org)
  • Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. (semanticscholar.org)
  • BACKGROUND BCR-ABL, a constitutively activated tyrosine kinase, is the product of the Philadelphia chromosome. (semanticscholar.org)
  • Safety and efficacy of blinatumomab in combination with a tyrosine kinase inhibitor for the treatment of relapsed Philadelphia chromosome-positive leukemia. (springer.com)
  • Because of the damage to the DNA, the Philadelphia chromosome results in the production of an abnormal enzyme called a tyrosine kinase. (verywellhealth.com)
  • The Philadelphia chromosome produces a tyrosine kinase protein called BCR-ABL1, and until recently this was considered the highest risk subset of pediatric ALL. (chop.edu)
  • Even in the tyrosine kinase inhibitor era, allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as standard care for adult Philadelphia (Ph) positive acute lymphoblastic leukemia (ALL). (diva-portal.org)
  • Frequency relapses are common in Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL) following tyrosine kinase inhibitors (TKIs). (biomedcentral.com)
  • The (9;22) translocation which produces the Philadelphia (Ph 1 ) chromosome activates the abl oncogene from chromosome 9 by recombination with the bcr gene from chromosome 22. (aacrjournals.org)
  • The result is that a fusion gene is created by juxtaposing the ABL1 gene on chromosome 9 (region q34) to a part of the BCR (breakpoint cluster region) gene on chromosome 22 (region q11). (wikipedia.org)
  • The translocation results in a p210 BCR-ABL fusion protein when the protooncogene ABL moves from chromosome 9 to the major breakpoint cluster region (M-bcr) within the BCR gene on chromosome 22 or in a shorter p190 BCR-ABL fusion protein when it moves to the minor breakpoint cluster region (m-bcr) within the same BCR locus. (bloodjournal.org)
  • Originally known as Supernumerary der (22) Syndrome, it occurs when an individual has an extra chromosome composed of pieces of the 11th and 22nd chromosomes. (wikipedia.org)
  • The symbol BCR is derived from breakpoint cluster region, a gene which encodes a protein that acts as a guanine nucleotide exchange factor for Rho GTPase proteins Translocation results in an oncogenic BCR-ABL1 gene fusion that can be found on the shorter derivative chromosome 22. (wikipedia.org)
  • Features associated with the presence of the Ph chromosome were high leukocyte count (median, 33 x 10 9 /L), older age (median, 9.6 years), a higher proportion of French-American-British L2 morphology, and a lower frequency of mediastinal mass. (elsevier.com)
  • Philadelphia chromosome-positive acute myeloid leukemia (Ph + -AML) has a poor response to anthracycline- and cytarabine-containing regimens, high relapse rate, and dismal prognosis. (jnccn.org)
  • Molecular characterization of Philadelphia chromosome-negative (Ph−) chronic myeloproliferative disorders, such as systemic mastocytosis (SM), has provided a clear rationale for investigating novel targeted therapies. (aacrjournals.org)
  • Later on, Janet Rowley at the University of Chicago proposed the molecular mechanism of Philadelphia chromosome translocation. (geneticeducation.co.in)
  • Changes to certain chromosomes are a prognostic factor for ALL. (cancer.ca)
  • abstract = "Among 3,638 children with acute lymphoblastic leukemia (ALL) entered on Pediatric Oncology Group (POG) protocols between June 1981 and April 1989, successful cytogenetic studies were available for 2,519, 58 (2.3%) of which had the Philadelphia (Ph) chromosome detected. (elsevier.com)
  • Coloured light micrograph of a female karyotype (chromosome set) with one defective chromosome each from pairs 9 and 22. (sciencephoto.com)
  • The 46 chromosomes of a human karyotype are here arranged in 23 pairs of a maternal and paternal chromosome. (sciencephoto.com)
  • Human chromosomes are numbered by their apparent size in the karyotype, with Chromosome 1 being the largest and Chromosome 22 having originally been identified as the smallest. (wikipedia.org)
  • Fingerprint Dive into the research topics of 'Philadelphia chromosome positive childhood acute lymphoblastic leukemia: Clinical and cytogenetic characteristics and treatment outcome. (elsevier.com)
  • Philadelphia chromosome positive acute myeloid leukemia (Ph+ AML) is a rare subtype of AML that is now included as a provisional entity in the 2016 revised WHO classification of myeloid malignancies. (ovid.com)
  • How we approach Philadelphia chromosome-positive acute lymphoblastic leukemia in children and young adults. (harvard.edu)
  • Successful treatment of a pregnant woman with Philadelphia chromosome-positive acute lymphoblastic leukemia. (biomedsearch.com)
  • Here, we report a case of a pregnant woman with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL) who underwent remission induction therapy and successfully delivered a live infant after chemotherapy. (biomedsearch.com)
  • Additionally, these kinases are key to the progression of CML and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). (nih.gov)
  • 6 Three percent of children who have ALL have the Ph+ subtype, which means they have a chromosome alteration that results in a specific mutation of the BCR-ABL gene. (businesswire.com)
  • BCR is well known because it becomes pasted onto Chromosome 9 in the classic leukemia mutation, the Philadelphia Chromosome . (genomeyear.net)
  • CML is caused by one translocation that creates a singular mutation, the BCR-ABL fusion gene or Philadelphia chromosome. (cancer.gov)
  • In the nucleus of each cell, the DNA molecule is packaged into thread-like structures called chromosomes. (verywellhealth.com)
  • He was rushed to The Children's Hospital of Philadelphia, along with my dazed husband. (chop.edu)
  • Children's Hospital of Philadelphia is a charitable 501(c)(3) nonprofit organization. (chop.edu)